Blood pressure and pulse were monitored throughout 24 hours in 13 middle-aged men using a sphygmomanometer with an automatically inflatable cuff. These volunteers were in part mistakenly believed to have a "mildly elevated blood pressure" (in the light of a conventional non-chronobiologic approach, involving timeunspecified spot checks of blood pressure). Within about 24 hours, blood pressures and pulse varied remarkably: the coefficient of variation extended from 6.9 to 14.9% for systolic blood pressure (SBP), from 8.5 to 15.4% for diastolic blood pressure (DBP) and from 8.0 to 17.9% for pulse. By applying the single cosinor method (involving the least-squares fit of a 24-hour cosine curve), statistically significant circadian rhythms were observed in SBP, DBP, and pulse in all but 2 cases. In most cases, the timing of peak values was estimated to be in the evening for all 3 variables. Circadian rhythmicity accounted for up to 46, 30, and 42% of the total variability of SBP, DBP, and pulse, respectively. This marked circadian rhythmic variability is an important aspect of cardiovascular function.

View full abstract

The present study was designed to examine whether the left atrium is dilated in paroxysmal atrial fibrillation or not. Left atrial dimension (LAD) on M-mode echocardiogram was (1) 23.3±0.7mm (mean ± S. E.) in 24 normal subjects, (2) 30.5±0.7mm in 58 patients without atrial fibrillation who had hypertension and/or ischemic heart disease, (3) 35.5±0.9mm in 27 patients with paroxysmal atrial fibrillation of whom 23 had non-rheumatic cardiovascular diseases and 4 had idiopathic atrial fibrillation, (4) 40.5±1.1mm in 38 patients with persistent atrial fibrillation of whom 30 had nonrheumatic cardiovascular diseases and 8 had idiopathic atrial fibrillation, and (5) 53.3±2.0mm in 17 patients with persistent atrial fibrillation who had rheumatic heart disease. LAD showed a stepwise and significant increase from the first to the fifth group. LAD of patients with paroxysmal atrial fibrillation was not related to either the number or duration of paroxysms. These results indicate that the left atrium is slightly dilated in patients with proxysmal atrial fibrillation.

View full abstract

Coarctation complex is a serious congenital cardiovascular malformation in infants. It is associated with severe congestive cardiac overload and high mortality even after surgical treatment.
To investigate left ventricular performance, quantitative morphometry and histometry of the left ventricle were carried out in 19 autopsied patients who died without surgical intervention. The following results were obtained:
1. Coarctation of the aorta was found to selectively affect the left ventricle, showing a volume overload response without effectively adapting to the pressure overload; the right ventricle showed a significant reaction to the pressure overload.
2. The coronary arterioles responded to the pressure load in the left ventricle.
In order to promptly recover left ventricular function, simple coarctectomy without VSD closure or other procedures is advisable for treatment of the coarctation complex in the early months of life.

View full abstract

Computed tomography (CT) of the lung in normal subjects and patients with congestive heart failure was performed in the supine position with deep inspiration to obtain pulmonary CT values and images. The mean CT value in normal subjects was higher in the posterior than anterior lung field, presumably because blood vessels were more dilated in the former than the latter due to the effects of gravity. The mean pulmonary CT value in patients with congestive heart failure was significantly increased possibly due to an increase in blood flow per unit lung volume arising from either pulmonary congestion or pulmonary interstitial and alveolar edema.
The mean pulmonary CT value increased parallel to the severity of pulmonary congestion, interstitial or alveolar edema and was well correlated with the pulmonary arterial wedge pressure, indicating that such a correlation was a valuable tool in assessing therapeutic effects.
The results of the present study indicate that pulmonary CT is useful for the noninvasive estimation of intrapulmonary water content and its distribution, thereby providing an effective diagnostic clue to various conditions in congestive heart failure.

View full abstract

The first heart sound was studied in 20 normal subjects. The phonocardiogram (PCG) was recorded from apical and mid-precordial areas using microphone with a flat response curve from 0.2 to 8, 000Hz. It was stored, together with a simultaneous electrocardiogram, on an FM analog tape recorder (linear frequency response from 0 to 4, 000Hz), fitted with a filter with weighting curve B according to the American National Standard Institute. A linear (SPL) recording was also made. The signal was fed through a digital converter into a minicomputer and the frequency distribution of the first heart sound was analyzed using Fast Fourier Transform. These data were stored and the average spectra were calculated for both B and SPL. The SPL spectra from both apex and mid-precordium showed a maximum intensity of about 80 dB between 12-20Hz, decreasing progressively to a constant level of 35 dB between 110-120Hz. The spectra obtained from both areas using filter B showed a maximum intensity of 40-50dB between 20-60Hz, decreasing to 30dB at 112Hz and remaining constant thereafter. It is important to emphasize that the dB values in B and SPL are absolute, since they refer to a standard reference weighting.
It appears that the SPL recording is more valuable in that it allows the study of all components of the PCG signal. The spectra obtained in this study will be used as a standard for future research in various pathological conditions.

View full abstract

The importance of metals in normal and pathologic cardiovascular function has been recognized. Significant derangements in myocardial Ca²⁺, Mg²⁺, and Cu²⁺ have been reported in ischemic heart injury. We studied 3 groups of hearts: 1) fifteen specimens obtained from patients who had no heart disease, 2) nine specimens from patients who had expired from cyanotic congenital heart disease, and 3) ten specimens from patients who had expired from acute rheumatic heart disease with carditis and severe heart failure. None of the patients had undergone cardiac surgery. Left ventricular lateral wall Mg²⁺, Ca²⁺, Cu²⁺, and Zn²⁺ contents were measured by atomic absorption spectrometry. The results showed a significant decrease in myocardial Mg²⁺ (Group I 177.06±32.71; Group II 155.66±14.79; Group III 149.00±13.29, p<0.05 and p<0.01, respectively), and Cu²⁺ contents (Group I 3.22±0.37; Group II 2.94±0.22; Group III 2.56±0.32, p<0.02 and p<0.001, respectively), and a rise in myocardial Ca²⁺ content (Group I 36.06±10.72; Group II 43.22±7.01; Group III 46.30±4.85, p=not significant, and p<0.01, respectively). The myocardial Zn²⁺ content did not change significantly (Group I 26.53±3.99; Group II 26.00±4.15; Group III 26.40±3.53). The myocardial Mg²⁺/Ca²⁺ ratio was reduced markedly in both groups (Group I 5.328±1.879; Group II 3.685±0.735; Group III 3.135±0.291, p<0.001 for both Groups II and III vs Group I). The latter results correlated closely with the myocardial Mg²⁺/Ca²⁺ ratios reported in experimental models in peri-infarction zones. Thus, the myocardium of patients who had expired from cyanotic congenital heart disease and acute rheumatic carditis is jeopardized by ischemia, with metal contents similar to the border areas in myocardial infarction.

View full abstract

Among 854 coronary angiograms, we found the following abnormalities of the coronary arteries. Three cases had nonatherosclerotic coronary artery aneurysms. One case, a 27-year-old man with a diffuse lesion, expired after two episodes of myocardial infarction. In 2 other cases the lesions were localized and the patients underwent successful coronary bypass surgery. In 2 cases, a small vascular network was found: a 23-year-old man with pheochromocytoma who also had myocardial injury and pulmonary edema, and a case with contusio cordis who had angina pectoris but had normal coronary arteries. In 3 cases the coronary arteries originated abnormally from the aorta. A congenital right coronary artery-right ventricular fistula was detected in a 17-year-old female with multiple cardiac abnormalities. Abnormally wide coronary arteries were also found in 17 cases with apical hypertrophy, a form of hypertrophic nonobstructive cardiomyopathy.

View full abstract

The effects of intravenous administration of mexiletine on the refractory periods of the atrium and atrioventricular (AV) node were studied using His bundle recordings and the extrastimulus technique with atrial pacing. The drug was administered to 10 children with heart disease in an intravenous bolus dose of 3mg/Kg, injected over a 5-min period, followed by an infusion of 1mg/Kg/hr of mexiletine, achieving a mean therapeutic plasma concentration of 0.762±0.270μg/ml. The AH and HV intervals, the resting sinus cycle length, and the functional and effective refractory periods of the atrium and AV node were measured before and 5min after initiation of the mexiletine infusion. The sinus cycle length was reduced significantly. However, neither the refractory periods nor the AH and HV intervals changed in a significant manner. Except for the heart rate, these results are similar to those reported in adults without conduction disturbances. In adults, mexiletine did not affect the sinus cycle length. However, in children, it consistently increased the heart rate. The lack of side effects in children is in contrast to adults, who usually suffer from gastrointestinal and neurologic symptoms upon receiving comparable doses parenterally.

View full abstract

Nitroglycerin ointment and nifedipine were used concurrently for vasodilator therapy in 10 patients with acute myocardial infarction. Nitroglycerin ointment 20mg (4cm) induced a significant reduction in pulmonary capillary wedge pressure from 14.1±1.8 (mean±standard error of the mean) to 12.4±1.2mmHg (p<0.05) 30min after application, while cardiac output, mean blood pressure, and systemic vascular resistance did not show a significant change. When nifedipine 10mg was added orally, mean blood pressure significantly decreased from 99.0±6.3 to 82.8±5.9mmHg (p<0.005) and systemic vascular resistance from 25.7±1.5 to 19.2±1.6 units (p<0.001) 30min after; on the other hand, cardiac index significantly increased from 2.28±0.12 to 2.57±0.141/min/m² (p<0.001). From these results, it was concluded that combined use of these two drugs was a useful and safe form of unloading therapy.

View full abstract

Left ventricular systolic pressure volume area (PVA) has been proposed as a reliable predictor of cardiac oxygen consumption per beat (VO₂). PVA is the area in the pressure-volume (P-V) diagram that is circumscribed by the end-systolic and end-diastolic P-V relation curves and the systolic segment of the P-V loop trajectory. It represents the total mechanical energy required for the ventricle to contract, to change its wall's elastic state from end diastole to end systole, and to eject blood against afterload. PVA has so far been measured manually with a planimeter applied to the P-V diagram. To measure PVA more accurately and on line during experiments, we devised a new method of computing PVA with a digital computer. The method consists of integrating during systole the infinitesimally narrow triangular pressure volume area swept by the straight line segment connecting Vd (ventricular volume at which peak isovolumic pressure is zero) and the instantaneously counterclockwise moving P-V data point in the P-V plane, and adding a small area between the end-diastolic P-V relation curve and the line connecting Vd and the end-diastolic P-V point. This method has proved useful in our study of the relation between VO₂ and PVA to evaluate the PVA's ability to predict VO₂.

View full abstract

Using mongrel dogs, an experimental study was performed to investigate Qs/Qt during v-v bypass with or without oxygenation. During bypass, the systemic circulation was maintained under constant conditions, while bypass flow rate, Svo₂ and Pvco₂ varied independently.
The results were as follows:
1) In dogs undergoing v-v bypass without oxygenation, Qs/Qt and A-aDO₂ increased markedly in proportion to bypass flow in animals receiving blood infusion into the right ventricle, but a remarkable increase was not seen in animals receiving blood infusion into the right atrium. The pulmonary artery waveform appeared to influence Qs/Qt.
2) A significant positive correlation was found between Qs/Qt and Svo₂. A-aDO₂ showed no correlation to Svo₂.
3) The Qs/Qt showed no remarkable changes despite significant changes in Pvco₂ (from 22 to 96mmHg).
4) With regard to Qs/Qt and Svo₂, it may be proper to perform v-v bypass at a flow rate of 30ml/Kg/min with blood infusion into the right atrium.

View full abstract

Electrical shock stimulation of the conotruncal area induced a spectrum of double outlet right ventricle (DORV) in embryonic chicks at developmental stages 24-27. The device used to apply electrical potentials to the heart was constructed using a 9 battery, a push-button switch, and a 100ohm, ten-turn potentiometer with a calibrated dial. The potentiometer was connected as a voltage divider with the outlet connected to an electrode pair. This allowed for a short voltage pulse (variable 0 to 9) to be applied to a selected area of the heart through the electrodes. Two different methods were chosen to apply electrical shocks to the conotruncal area of the heart. One method utilized the application of an electrical shock between two points across the conotruncus of cardiac loop (horizontally oriented) and the second method between two points along the conotruncus of cardiac loop (vertically oriented).
The range of voltages applied to the conotruncal area of the heart was from 2 to 4. Three distinct types of double outlet right ventricle were in the longitudinal (L) and horizontal (H) electrical shock groups:
1) DORV without a ventricular septal defect (VSD), which is associated with a prolapse of an aortic valve into the right ventricle (5/50 cases in L group, 3/40 cases in H group).
2) DORV with a subaortic VSD, with a variable degree of pulmonary stenosis and a hypoplastic left ventricle (20/50 cases in L group, 12/40 cases in H group).
3) DORV with a subpulmonary VSD and a pulmonary stenosis, c hypoplastic right ventricle (15/50 cases in L group, 5/40 cases in H group).
Longitudinal stimulation induced more cardiovascular anomalies than horizontal stimulation, and histological examination revealed the complete disappearance of the myocardial fibers, myocardial degeneration, and the aggregation of protein material or glycogen in the myocardial cells. The relationship between cell death processes in the conotruncal area and the DORV spectrum induced by electrical shock are discussed.

View full abstract

In the perfused rat mesenteric vascular bed, the effects of magnesium and calcium on the vasoconstrictor responses to norepinephrine or potassium chloride were studied. Higher concentrations of magnesium in the perfusate attenuated the vascular responses to norepinephrine and potassium chloride in a dose-related manner. Higher concentrations of calcium in the perfusate enhanced greatly the vascular responses to potassium chloride, while the response to norepinephrine was only slightly potentiated by increasing calcium concentration. The attenuating effect of magnesium on the responses to norepinephrine and to potassium chloride were reversed by elevation of calcium concentration in the perfusate. The potentiating effects of calcium on the responses to potassium chloride were also reversed by increasing the concentration of magnesium. However, an inhibitory effect of magnesium on the responses to norepinephrine was not observed in the presence of higher concentrations of calcium. These results indicate that magnesium acts antagonistically on calcium movement in vascular contractions due to potassium chloride, but that the relationship between magnesium and calcium is more complex in vascular contractions induced by norepinephrine.

View full abstract

As glucose-insulin-potassium solution (GIK) has been used as clinical cardioplegia during open heart surgery, we studied the fundamental effects of GIK on the electrical and mechanical activities of the bullfrog atrial muscle under voltage clamped and unclamped conditions by the double sucrose-gap method. GIK produced an immediate disappearance of the action potential and twitch tension with pronounced depolarization accompanied by transient contracture. Reperfusion with normal Ringer's solution after GIK perfusion (30-180min) resulted in recovery of the action potential, with an initial lengthening followed by a sustained shortening in duration. Recovery of twitch tension was incomplete, and perfusion with GIK for a longer period caused stronger suppression. Voltage clamp studies revealed that after removal of GIK, the slow inward current (I_s) and I_s-dependent tension were markedly depressed, while the delayed outward current (I_x) was augmented. The fast inward current (I_Naf), background current (I_k1), and I_s-independent tension gradually recovered to the control levels. Perfusion with low Ca Ringer's solution or verapamil Ringer's solution for 10min at the initial reperfusion phase significantly improved the recovery of I_s and the I_s-dependent tension. These results indicate that the after-effects of GIK are mainly governed by Ca influx at the initial reperfusion phase. Therefore, a lowering of the Ca influx in this period is expected to produce a beneficial effect on cardiac function after GIK treatment.

View full abstract

In an attempt to elucidate the characteristics of the metabolic response of the hypertrophying heart, the rates of amino acid incorporation into cardiac structural proteins were studied in female rabbit hearts in vivo by use of a pulse-label isotope (³H-lysine) method. Hypertrophy of the left ventricle was produced by applying mild aortic constriction. Structural proteins were separated from the heart excised 24h after the pulse, and the rate of ³H incorporation was calculated as cpm ³H/mg lysine of the protein. In the control (without aortic constriction), left ventricular structural proteins exhibited the following relative incorporation rate (the rate in actin being taken as 1.0): native tropomyosin, 2.79±0.38 (mean±SE, n=5); 10S-actinin and α-actinin complex, 2.52±0.29; heavy chain of myosin, 2.09±0.25; light chain of myosin, 1.82±0.28; soluble protein, 1.79±0.30; and actin, 1.0. In the rabbits with aortic stenosis the rates of amino acid incorporation showed a striking increase up to 7 days after surgery, and declined to the control level by 1 month. Among the protein fractions, native tropomyosin and the light chain of myosin showed a much higher rate of isotopic incorporation during the earlier phase of the response. These results seem to indicate the presence of a unique pattern of metabolic response in cardiac muscle confronted with a workload.

View full abstract

Effects of regional ischemia on myocardial glycolysis were studied by measuring the levels of glycolytic intermediates in the endo- and epicardial layers of the left ventricle in dogs anesthetized with pentobarbital. Regional ischemia was induced by ligating a small branch of the left anterior descending coronary artery. The myocardial tissue samples were removed before and 1.5, 3, 7, or 30min after coronary artery ligation. Based on a crossover plot study of the glycolytic intermediates, it is suggested that the activity of glycogen phosphorylase was accelerated, while that of phosphofructokinase was inhibited in ischemic myocardium samples removed 1.5, 3, 7, and 30min after ligation. When the frozen myocardium was allowed to stand at room temperature for 10min, the crossover plot study revealed acceleration of phosphofructokinase activity. The metabolic response to regional ischemia of the endocardial layers was more marked than that of the epicardial. During ischemia the levels of adenine nucleotides did not change significantly, but those of citrate and hydrogen ions increased significantly. It appears that inhibition of myocardial phosphofructokinase activity during ischemia is partly due to an increase in the levels of citrate and hydrogen ions in the ischemic tissue.

View full abstract

Calcium-activated neutral protease (CANP) might be involved in the irreversible degradation of myocardial proteins in the ischemic region, leading to the loss of contractility. The new compound, NCO-700, and its analogues were synthetized against CANP. Among these analogues, NCO-700 was the most potent to reduce the size of acute myocardial infarction, which was produced by coronary artery ligation in rabbits, in vivo, although it showed less powerful action to inhibit CANP activity in vitro. The new reagent, NCO-700 might be promising to reduce acute myocardial infarction size and beneficial for the clinical studies, because it had no action to reduce cardiac muscle contractility, compared with beta antagonist or calcium-channel blockades.

View full abstract

Acute myocarditis is produced in rabbits with scorpion (Buthus tamulus) (a common scorpion found in South India) venom. Acute myocarditis is confirmed by changes in the ECG taken before and after venom injection. The atrial and ventricular sarcolemmal Na⁺-K⁺ ATPase, Mg⁺⁺ ATPase, and Ca⁺⁺ ATPase activities are assayed in control and venom injected rabbits. Atrial and ventricular sarcolemmal ATPase activities are similar in control animals. A significant reduction in atrial Ca⁺⁺ ATPase activity is seen in venom treated rabbits. Animals injected with 2mg/Kg venom exhibited significant increases in Mg⁺⁺ ATPase and Ca⁺⁺ ATPase activities in the ventricular sarcolemma. However, significant reductions in Na⁺-K⁺ ATPase and Ca⁺⁺ ATPase activities are observed in ventricular tissue from rabbits treated with 4mg/Kg of venom.

View full abstract

Clinical, hemodynamic, electrocardiographic (ECG), echocardiographic, left ventricular (LV), and coronary angiographic (CA) findings are reported in a case with apical hypertrophy (AH), a form of hypertrophic nonobstructive cardiomyopathy (HNCM). The most striking symptom was chest pain and the most conspicuous electrocardiographic finding consisted of giant negative T waves, reaching an amplitude of 4.0mV. Echocardiography revealed an apical thickness of the septum and posterior wall of 40mm; this was significantly greater than septal and posterior free wall thickening in the LV outflow area. The anterior motion (SAM) of the anterior mitral leaflet, was present, and, in hemodymic investigation, the isoproterenol test was negative. The left ventricular enddiastolic pressure (LVEDP) and the EF were elevated. In the LV angiogram from the right anterior oblique position (RAO), the LV free wall thickness at the apex was significantly thicker than at the outflow tract level. The patient had dilated coronary arteries.
We conclude that these findings are typical for AH (HNCM) and it seems that hypertrophic obstructive cardiomyopathy (IHSS, MO), and hypertrophic non-obstructive cardiomyopathy (ASH, AH) are different manifestations of a wide spectrum of hypertrophic cardiomyopathy.

View full abstract