Alpha human atrial natriuretic polypeptide (α-hANP) was intravenously infused into 7 patients with ischemic heart disease who had almost normal cardiac function at a rate of 0.025 μg/kg/min for 15 min. During infusion of α-hANP, left ventricular (LV) systolic pressure decreased from 144 ± 19 (SD) to 129 ± 22 mmHg (p < 0.01), LV end diastolic pressure (EDP) from 15 ± 5 to 13 ± 4 mmHg (p < 0.05), mean aortic pressure from 102 ± 14 to 91 ± 14 mmHg (p < 0.01), time constant of LV pressure fall (T) from 100 ± 15 to 88 ± 13 msec (p < 0.05), systemic vascular resistance (SVR) from 1711 ± 206 to 1424 ± 340 dynes·sec·cm^-5 (p < 0.05) and coronary vascular resistance (CVR) from 8.5 ± 1.2 to 7.4 ± 1.3 × 10⁴ dynes·sec·cm^-5 (p < 0.05). There was a linear correlation between percent changes in SVR and those of CVR (r=0.92, p < 0.01), and the fall in CVR was approximately 68% of that in SVR. Increases occurred in heart rate from 63 ± 7 to 66 ± 8 beats/min (p < 0.05), LV dp/dt from 1558 266 to 1627 238 mmHg/sec (p 0.05), LV dp/dt/p from 22.9 3.2 to 25.6 3.7/sec (p 0.01), and myocardial oxygen consumption (from 7.9 2.4 to 9.8 2.1 ml/min, p 0.05), while mean right atrial and mean pulmonary arterial pressures and pulmonary vascular resistance were unchanged. -hANP dilates the systemic and coronary resistance vessels, and increases myocardial shortening velocity and relaxation.

View full abstract

New criteria for the diagnosis of right ventricular hypertrophy (RVH) using a point scoring system were developed after analyzing standard 12-lead ECGs in 155 patients with mitral stenosis verified by cardiac catheterization and 155 age and sex-matched apparently normal healthy subjects. ECGs were evaluated to identify criteria that provided maximum sensitivity and at least a 95% specificity: (1) the R wave magnitude in V₁ had to be > 0.7 mV; (2) the S wave magnitude in V₆ had to be > 0.3 mV; (3) the S wave magnitude in V₁ < 0.5 mV; (4) the R wave magnitude in V₁ plus the S wave magnitude in V₆ minus the S wave magnitude in V₁ must be > 0 mV; and (5) the degree of frontal QRS axis had to be > 90°. Application of these criteria achieved 25% (39 of 155) sensitivity in patients with RVH, significantly better (p < 0.01) than the 17% sensitivity (17 of 155) of Bonner's criteria for the automated ECG. The specificity of the proposed criteria was 98% (152 of 155), significantly better (p < 0.01) than the 90% specificity (139 of 155) of Mortara's criteria. Thus, it was evident that the accuracy of the proposed criteria was the highest among those criteria used in a point scoring system including the currently used automated ECG criteria for the diagnosis of RVH.

View full abstract

The relationship between echographical cardiac function and sympathetic nerve activity during dynamic exercise was examined in patients with essential hypertension. Nine normotensives (Group N), 11 hypertensive patients without cardiac hypertrophy (Group NH) and 13 hypertensive patients with cardiac hypertrophy (Group HH) were studied during multistage exercise using a supine bicycle ergometer. The shortening fraction (SF) and the peak negative dD/dt in Group HH, being within the normal range, tended to be samller than those in Group N at the 75-watt load. The mean value of the peak positive dD/dt (+dD/dt) in Group HH was significantly smaller than that in Group N at rest and during the 75-watt load. The percent increase of plasma norepinephrine (NE) levels (%ΔNE) at the 75-watt load was significantly greater in Group HH than in Group N. Plasma NE, in some patients with cardiac hypertrophy and compromised cardiac function, markedly increased (%ΔNE &ges; 186) during exercise. %ΔNE was directly related to the left ventricular mass index among all of the groups, but it was inversely related to the SF, -dD/dt, and to +dD/dt at the 75-watt load. We conclude that the augmented sympathetic nerve activity may contribute to preserving left ventricular systolic function during exercise within the normal range in hypertensive patients with cardiac hypertrophy.

View full abstract

We analyzed transmitral flow using pulsed Doppler echocardiography during anginal attack provoked by atrial pacing in 11 patients with coronary artery disease (CAD). Left ventricular (LV) filling period was divided into 4 time intervals (Tr1: the time interval to peak velocity of rapid filling (peak R), Tr2: the time interval from peak R to the end of rapid filling, Ts: the time interval of slow filling, Ta: the time interval of atrial contraction). The velocity in each interval was integrated by planimeter as IR1, IR2, IS or IA which indicates relative filling volume in each interval. During angina, IR1 was unchanged due to prolongation of Tr1 (82 ± 12 to 102 ± 23 msec, p < 0.02), despite a decrease in peak R (54 ± 11 to 43 ± 11 cm/sec, p < 0.005), while IR2 decreased (5.8 ± 1.9 to 4.3 ± 1.4 cm, p < 0.005) and IA increased (6.7 ± 1.4 to 7.3 ± 1.3 cm, p < 0.005). In conclusion, these results suggested that in acute myocardial ischemia in CAD a decrease in trasmitral flow from the time of peak R to the end of rapid filling (IR2) reflected the impairment of the LV rapid filling, which was incompletely compensated by an increase in atrial contraction.

View full abstract

Left ventriculograms were performed on 65 patients with acute myocardial infarction, once upon admission and again 3 months later. In 29 cases urokinase was injected intravenously and/or intracoronarily. The other 17 were treated without urokinase. In 8 out of 29 patients whose infarct-related coronary arteries remained completely occluded following urokinase therapy, the global ejection fraction was reduced from 54 ± 3% during the acute stage to 46 ± 5% during the chronic stage (p < 0.001). However, for the 21 patients whose coronary arteries were successfully recanalized, the 2 values were the same (52 ± 2%). The highest global ejection fractions were seen in 19 spontaneously recanalized patients (acute: 54 ± 2%, chronic: 55 ± 2%). For the 8 unsuccessful patients, the regional ejection fraction for the infarcted portion was reduced from 20 ± 5% during the acute stage to 18 ± 6% during the chronic stage. But for the successful patients there was an improvement from 22 ± 2% during the acute stage to 27 2% during the chronic stage. Again, the regional ejection fraction was the highest for the spontaneously recanalized group, being 31 2% and 36 3% during the acute and chronic stages, respectively. These results indicate that if the coronary artery remains occluded during the acute stage the reduced left ventricular function continues to deteriorate even more during the chronic stage. Successful coronary thrombolysis, however, might salvage the infarcted myocardium as well as preserve the function of the left ventricle.

View full abstract

The serial change in left ventricular function was investigated by radionuclide angiocardiography in 25 patients undergoing coronary artery bypass grafting (CABG). Multiple gated equilibrium blood pool imaging was performed at rest before, and at 1, 2 and 4 weeks after the operation and also during exercise on a supine bicycle ergometer before and 4 weeks after surgery. Global ejection fraction at rest was unchanged after CABG while peak ejection rate increased significantly at 1 and 2 weeks (p < 0.01 and p < 0.05 respectively) after the operation .Peak filling rate at rest was generally unchanged after surgery but peak filling rate during the first third of diastole at rest decreased significantly at 1 and 2 weeks (p < 0.01 and p < 0.05). After CABG, the increases in ejection fraction and peak ejection rate with exercise were significantly greater than those values measured before surgery. The increases, due to exercise, in peak filling rate and peak filling rate during the first third of diastole were unchanged after the operation. Radionuclide angiocardiography affords a safe, noninvasive, and highly reproducible procedure for serially assessing ventricular function in patients undergoing CABG. Our study revealed early diastolic dysfunction within 2 weeks of surgery and that CABG abolished abnormalities in left ventricular function induced by exercise.

View full abstract

We performed gross-anatomic and histologic examinations quantitatively on 18 male and 30 female WKY/NCrj rats, and their 299 first generation off spring. The results were analyzed in comparison with those obtained from 3 other strains of rats. The offspring of the WKY rats showed various cardiac abnormalities quite similar to those in their parents. The cardiac abnormalities in the offspring of the WKY rats were: increased heart weight (in about 10%), left or right atrial hypertrophy (50%), disproportionate septal thickening (50%), small left ventricular cavity (40%), right ventricular hypertrophy (40%), abnormal fiber arrangement greater than 5% in either of the 3 ventricular walls (90%), myocardial fibrosis (70%), and abnormal location of arteries in the ventricular septum (30%). ECG findings of the WHY-F rats such as high QRS complexes and high T waves and axis deviation showed a high sensitivity and specificity in the diagnosis of marked cardiac hypertrophy. Another consipicuous histologic finding observed in the WKY hearts was that the continuity of the latitudinal fiber bundle of the ventricular septum with that of the left ventricular free wall, an important functioning unit for pressure generation in the left ventricle, was markedly disturbed in the area of junction between the 2 walls; the smaller the continuity, the greater the cardiac hypertrophy; the disadvantage of the discontinuity for the pressure generation may be related to the development of cardiac hypertrophy. Also examined were two strains of Wistar rats with the same origin as the WKY/NCrj. These rats also had gross-anatomic and histologic abnormalities of the heart quite similar to those in he 2 generations of WKY/NCrj rats, suggesting that a common factor related to the development of the abnormalities, probably a genetic predisposition, has been transmitted in these 3 strains.

View full abstract

In order to treat acutely uremic patients in an unstable hemodynamic state, we developed a new system for slow continuous hemodialysis. It is well known that continuous hemofiltration or peritoneal dialysis are successful in terms of removing the excess body water without adverse effects on hemodynamics. On the other hand, hemodialysis is far more effective in eliminating solutes such as uremic toxins, especially under a catabolic state. In order to combine the merits of both interventions, volume control and solute removal were dealt with separately in our system. The main system is composed of a double-pump driven closed circuit for the re-circulated hemodialysis. Volume control was achieved accurately within ±5% error of the set rate. The dialysance was evaluated in vitro and the efficacy of solute elimination was simulated mathematically. It was speculated that slow continuous hemodialysis could be a new method of treating critically ill patients with acute renal failure.

View full abstract

Five acutely uremic dogs were treated for 9 hours by means of slow continuous hemodialysis using our newly developed machine. The blood concentrations of urea nitrogen (BUN) and creatinine were determined every hour and were compared to those calculated from a mathematical pool model. In order to assess the accuracy of volume control, the body weight of dogs was monitored continuously by scale bed, under simultaneous 200 ml/hour infusion and ultrafiltration. Arterial and swan-ganz catheter were inserted to measure hemodynamic changes during hemodialysis. The efficacy of solute elimination was coincidental with the predicted value. The error of volume control was within ±5% of set rate. Hemodynamic parameters were not significantly influenced in spite of a large amount of volume exchange. In conclusion, it was demonstrated that slow continuous hemodialysis could be a better alternative to peritoneal dialysis, continuous hemofiltration or conventional hemodialysis in order to treat acute renal failure in critically ill patients, in terms of solute removal, volume control and the effects on hemodynamics.

View full abstract

Recently, we demonstrated that more β-type myosin heavy chain (HC) was expressed in the overloaded atrium, and that there were 2 structurally different β-type myosin heavy chains in the bovine heart. To determine the existence of the 2 β-type HC in other animals and to clarify the characteristics of these β-type HCs, we produced tricuspid regurgitation and pulmonary stenosis in the canine heart, and performed an immunological study using 3 monoclonal antibodies, 2 β-type specific antibodies (HMC14 and 50) and 1 α-type specific antibody (CMA19). In an immunohistochemical study, serial cryostat sections revealed that some myofibers reacted with HMC50 (HCβ2), but almost no fibers were labeled with HMC14 in the normal atrium. However, in overloaded atria, not only HCβ2 but the HC, reacted with HMC14 (HCβ1). By affinity chromatography, HCβ2 was fractionated from normal atrial myosin using HMC50 and HCβ1 was fractionated from overloaded atrial myosin using HMC14. These 2 HCβ's were subjected to digestion by -chymotrypsin, staphylococcus aureus V8 protease, and cyanogen bromide, and proved to have different peptide fragments. In respect to enzymatic properties, the Ca²⁺-activated ATPase activities of HC1 and 2 were almost the same but lower than that of HC. We concluded that the isozymic transition of HC to HC in the atrium was experimentally induced by hemodynamic overload and that HC1, which was hardly recognized in the normal atrium but highly induced by overload, was structurally different from HC2, as expressed in the normal atrium.

View full abstract

The acute effects of the selective alpha₁-blocker, E-643 (Bunazosine), on experimental pulmonary hypertension (PH) caused by hypoxic pulmonary vasoconstriction (HPV) in mongrel dogs were examined .Ninety second ventilation with 5% O₂ and 95% N₂ was used for hypoxic stimulation .The effects of E-643 were evaluated at doses of 1, 5, 10, 20 and 50 μg/kg in this order until the systemic arterial mean pressure (SAm) had decreased by 20 mmHg when compared with the control value during room air ventilation. PaO₂ and PaCO₂ decreased by 64.6 ± 11.0 Torr and 2.4 ± 2.5 Torr, respectively, and the pH increased by 0.031 ± 0.012 during hypoxic ventilation. These blood gas changes affected during hypoxic stimulation were almost the same before E-643 administration. Progression of arterial blood hypoxemia due to E-643 administration during room air ventilation was not observed. SAm decreased by 8.0 ± 11.9 mmHg after E-643 administration, while left atrial mean pressure (LAm) and cardiac output (CO) did not change significantly. Prior to E-643 administration, mean pulmonary arterial pressure (PAm) and pulmonary vascular resistance (PVR) increased by 6.4 3.3 mmHg and 6.2 3.8 HRU, respectively, during the 90 sec hypoxic ventilation period. After E-643 administration, the increases in PAm and PVR were 3.9 1.7 mmHg and 3.3 2.3 HRU, respectively. The supression of increases in PAm and PVR was significant. The conclusion is that E-643, a selective alpha₁-blocker, is effective at restraining HPV in the dog model.

View full abstract

In order to assess myocardial hypertrophic activity during the process of hypertensive cardiac hypertrophy in the presence and absence of treatment with anti-hypertensive agents, we analyzed myocardial polyamine concentrations in spontaneous hypertensive (SHR) rats and control rats of Wistar Kyoto (WKY) strain. The anti-hypertensive agents studied were diltiazem, hydralazine and captopril, each of which was administered for 5 weeks. In comparison with WKY rats, SHR rats showed elevated blood pressure and enlarged hearts with higher myocardial spermidine concentration. Although blood pressure was lowered in the diltiazem-treated SHR rats, heart weight and myocardial spermidine concentration increased as in untreated SHR rats. In the hydralazine-treated group increases in both blood pressure and myocardial spermidine concentration were all suppressed. Since spermidine level appears to be a sensitive indicator of hypertrophic activity in the heart, this study suggests that captopril exerts an inhibitory effect on hypertensive cardiac hypertrophy whereas diltiazem does not. It also suggests that hypertrophy may reach a certain plateau level earlier in the hydralazine-treated animals than in others.

View full abstract

We experienced a case of subclavian steal syndrome (SSS) with a specific form of obstruction of the right proximal subclavian artery. The patient was a 44-year-old man who complained of numbness of the right hand. Right carotid-subclavian artery anastomosis was performed under general anesthesia. The obstructed segment was a fibrous cord, 3.5 cm in length and 2.0 mm in diameter. Postoperatively, the patient was free from the symptom. In the Japanese literature, 73 cases of SSS were reported from 1965 to 1986, and the etiology was mentioned in 64 cases. In 28 cases the cause was aortitis syndrome (43.8%), in 22 cases arteriosclerosis (34.4%), in 13 cases congenital malformation (20.3%), and in 1 case iatrogenic lesion (1.6%). These data indicated that SSS caused by congenital malformation was not so rare as previously believed. Of 13 cases with congenital malformation, our case and 3 other cases had similar aspect in clinical features. All 4 patients were middle-aged men (aged 34, 26, 45 and 44 years) with a fibrous cord at the proximal portion of the right subclavian artery. None had any other cardiovascular anomalies.

View full abstract