The role of lipoprotein lipase and hepatic lipase in the conversion of LDL₁ (1.019<d<1.045) to LDL₂ (1.045<1.063) were investigated on the basis of incubation of ¹²⁵I-LDL₁ with postheparin plasma (PHP) at NaCl concentrations of both 0.15 M and 1.0 M. Insignificant small increments of radioactivity and apoprotein B specific activity of LDL₂ were observed even when ¹²⁵I-LDL₁ was incubated with preheparin plasma as the control. When ¹²⁵I-LDL₁ was incubated with PHP, the LDL₁ radioactivity decreased and the LDL₂ radioactivity increased significantly. The apoprotein B specific activity was also increased in the LDL₂ fraction. One molar NaCl did not inhibit these changes. It is concluded that hepatic triglyceride lipase was the major mediator in the conversion of LDL₁ to LDL₂.

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To investigate the pathophysiology of ischemic heart disease (IHD), tourniquet ischemia on the upper limb was done and changes in platelet aggregation, plasma 6-keto-PGF₁α concentrations and plasma thromboxane B₂ (TXB₂) concentrations were studied. At rest, platelet aggregability and plasma TXB₂ concentrations were significantly increased in IHD patients compared with those in normal subjects (p<0.001 and p<0.001, respectively). In normal subjects, platelet aggregability, plasma 6-keto-PGF₁α concentrations and plasma TXB₂ concentrations rose significantly during ischemia (p<0.05, p<0.02 and p<0.05, respectively). In addition, plasma 6-keto-PGF₁α concentrations were significantly lower in IHD patients than in normal subjects during ischemia (p<0.005), though there was no significant change in the level of either group at rest. These results suggest that increase in prostacyclin synthesis in normal subjects during tourniquet ischemia may be a defense mechanism to maintain the balance between prostacyclin and thromboxane A₂ (TXA₂) and to prevent platelet aggregation induced by the procedure. Increase in platelet aggregation and TXA₂ generation in IHD patients at rest indicates a close correlation between IHD and platelet reactivity. Tourniquet ischemia induced a significant increase in prostacyclin generation in normal subjects but not in IHD patients, which suggests that production of prostacyclin was impaired in IHD patients during ischemia. A marked difference was obvious in prostacyclin and TXA₂ generation between IHD patients and normal subjects, and this difference may play an important role in the pathogenesis of IHD.

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Twenty-nine anesthetized mongrel dogs were subjected to characterize the effect of lidocaine in ischemic reperfused myocardium. The left anterior descending coronary artery was ligated for 40 min and reperfused for 15 min. Two mg/kg of lidocaine was administrated intravenously prior to the ligation and 2 mg/min (= 0.12 mg/kg/min) was infused continuously throughout the periods of coronary artery ligation and the reperfusion. Hemodynamic indices of left ventricular function were measured before ligation, 40 min after ligation and after 15 min of reperfusion, respectively. Transmural myocardial samples obtained from both the ischemic and non-ischemic regions after 15 min of reperfusion were divided into the subendocardial and subepicardial layers and used for measurements of adenosine triphosphate (ATP), creatine phosphate (CP) and water content. ATP in ischemic endocardium was 1.73±0.69μmole/g in the lidocaine-treated group and 1.36±0.41 in the non-treated group (p<0.05), and CP was 2.38±0.90 μmole/g and 1.59±0.95, respectively (p<0.01). Thus, high energy phosphate was at a significantly higher level in the lidocaine-treated group. Water content was significantly higher level in the lidocaine-treated group as compared with the non-treated group. Coronary blood flow and left ventricular functions were not significantly different between the two groups. These data suggest that lidocaine has a protective effect on ischemic reperfused myocardium and does not depress the left ventricular function in the commonly used doses.

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Intracellular microelectrode recording techniques were used to elucidate the mechanism of the antiarrhythmic action of disopyramide in an isolated rabbit ventricular muscle perfused by hypoxic Tyrode's solution. Hypoxia induced no significant changes of the resting membrane potential or action potential amplitude but decreased the maximum upstroke velocity of the action potential (dV/dt max) and shortened the action potential duration and the effective refractory period. Disopyramide in a dose of 5 μg/ml induced a significant decrease of resting membrane potential and action potential amplitude of hypoxic muscle, while it did not alter these parameters in oxygenated muscle. Disopyramide depressed dV/dt max in hypoxic muscle as well as in oxygenated muscle. However, there was much greater depression in hypoxic cells. After disopyramide, action potential duration at the 90% level of repolarization and the effective refractory period were prolonged in both hypoxic and oxygenated ventricular muscle. However, disopyramide lengthened the effective refractory period of hypoxic muscle to a much greater degree than that of oxygenated muscle. This resulted in a decrease of disparity in refractoriness. The above differential effects of disopyramide i oxygenated and hypoxic tissue may account for its effectiveness in post-infarction re-entrant arrhythmias.

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In 1, 000 patients on whom vectorcardiography was performed, ventricular gradients (G^^&roarr;) were calculated using a micro-computer. In 73 patients, excluding those with dextrocardia and atrial fibrillation, the X component of the ventricular gradient ( Gx) showed a negative value. These patients with a negative Gx were divided into the following 10 subgroups and their G^^&roarr; were compared: hypertrophic non-obstructive cardiomyopathy (HCM), hypertrophic obstructive cardiomyopathy (HOCM), congestive cardiomyopathy, concentric left ventricular hypertrophy, aortic valvular disease, ischemic heart disease, myocardial infarction, pericarditis, right ventricular hypertrophy and others. The HCM group was the most characteristic with large A^^&roarr;qrs oriented to the left, the largest A^^&roarr;t oriented to the right and the largest G^^&roarr; oriented to the right. Gx in this group showed values more negative than -50 μV·sec (-92.2±32.0) and significantly differed from other groups.

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Factors affecting the surgical results of total anomalous pulmonary venous drainage were evaluated in 17 patients in an attempt to establish an appropriate plan of management. The mortality rate correlated with age, size of interatrial communication, arterial oxygen saturation and left heart volume but not with pulmonary to systemic systolic pressure ratio, vascular resistance ratio and right ventricular volume. In cases where the symptoms appeared early in life, left heart volume was small and clinical features were severe. Four children with a left ventricular end-diastolic volume of less than 65% of normal died of low cardiac output syndrome. In those with an unusually small left heart, enlargement of the left atrium and/or delayed ligation of the anomalous vertical vein were considered more favorable. Left atrial and ventricular volumes were restored to normal after the surgery.

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A correlative study was performed on 70 patients with old anterior myocardial infarction between each of the orthogonal components of instantaneous QRS vectors and the anterior-wall, lateral-wall and septal myocardial uptake ratios (A-MUR, L-MUR and S-MUR, respectively). These MURs were calculated from the thallium-201 myocardial perfusion images at 5 projections and used as the index of the infarct size of the respective LV wall. The Z components of the 14-msec and 24-msec instantaneous QRS vectors significantly correlated with the S-MUR (r = -0.51) and the A-MUR (r = -0.66) respectively. The X component of the 32-msec instantaneous QRS vector also showed a significant correlation with the L-MUR (r = 0.59). The regression equations obtained in the present study seemed also applicable to patients with complete right bundle branch block. It is concluded that the quantitative analysis of the Frank vectorcardiograms could afford valuable information as to the size as well as the site of myocardial infarctions.

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The electrophysiological effects of intravenous administration of disopyramide (1.5 mg/kg) were studied in 26 patients with sinus node dysfunction (SND). Disopyramide shortened spontaneous cycle length (SCL) in 12 patients and lengthened it in 4. Maximum sinus node recovery time (max SRT) was prolonged in 9 patients and shortened in 6. Estimated sinoatrial conduction time (SACT) was prolonged in 4 and shortened in 4 out of 10 patients in whom this measurement was possible. However, these changes in PA and AH intervals significant. Neither were there any significant changes in PA and AH intervals nor refractory periods of the AV node. HV intervals and refractory periods of the atrium at matched cycle length were significantly lengthened. Atrial echo beats and atrial premature beats disappeared in 7 of 12 patients treated with disopyramide. In all of these 7 patients atrial refractory period were increased. Thus, the disappearance of atrial echo beats and atrial premature beats was thought to be due to a prolonged atrial refractoriness. In 4 patients who had supraventricular arrhythmias without having either marked prolongation of max SRT or episodes of syncope, disopyramide was administered orally for a long term, during which these arrhythmias and symptoms disappeared and sinus rate increased. These results suggest that disopyramide is useful in patients with SND and supraventricular arrhythmias.

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A 21-year-old female was diagnosed as having a triad of interruption of the aortic arch, patent ductus arteriosus and ventricular septal defect. The patient died from bacterial endocarditis associated with acute peritonitis and perirenal abscess at the age of 31. This is the third longest survival of a case affected with the above triad, as far as we know.

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Captopril was administered to acute (8 to 14 days after unilateral renal artery constriction) and chronic (71 to 127 days after the constriction) two-kidney Goldblatt hypertensive dogs, and to normotensive ones for 21 days (oral administration of 10, 20 and 40 mg/kg/day, consecutively each 7-day period). The decrease of arterial blood pressure was remarkable in hypertensive animals with high plasma renin activity, but not in the normotensive animals. In the acute stage of hypertension, the antihypertensive effect of captopril was dose-dependent and persistent even after its cessation. In the chronic stage of hypertension, blood pressure also decreased, but the response was not dose-dependent and did not continue after cessation. Plasma renin activity rose in both hypertensive and normotensive animals during the treatment with captopril. There were no significant changes in heart rate, daily urinary volume, sodium balance, and renal clearances of sodium (C_Na), potassium (C_K), chloride (C_Cl) and creatinine (C_Cr). Circulating blood volume was also not altered. These results indicate that the main mechanism of antihypertensive effect of captopril in two-kidney Goldblatt hypertensive dogs is an inhibition of the angiotensin converting enzyme. In addition, the different effects in the acute and chronic hypertensive dogs suggest that some differences exist in the mechanism(s) of maintaining blood pressure between the two stages of two-kidney Goldblatt hypertension in dogs.

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Thallium-201 myocardial scintigraphy was performed on 55 patients with various types of right ventricular overloading. The right ventricular (RV) free wall was visualized in 39 out of the 55 patients (71%). The mean values of right ventricular systolic pressure (RVSP) and pulmonary artery mean pressure (PAMP) in the visualized cases (uptakers) were 54.6±24.1 and 30.5±15.3 mmHg, respectively. These values were significantly higher than those of the non-visualized cases (non-uptakers). There were 12 RVSP-"normotensive" uptakers and 15 PAMP-"normotensive" uptakers. The RV free wall images were classified into three types according to their morphological features. Type I was predominantly seen in cases of RV pressure overloading, type II in RV volume overloading and type III in combined ventricular overloading. RVSP in the type III group was significantly higher than that in other two groups. The radioactivity ratio in RV free wall and interventricular septum (IVS), the RV/IVS uptake ratio was calculated using left anterior oblique (LAO) view images. The RV/IVS uptake ratio closely correlated with RVSP and PAMP (r = 0.88 and 0.82, respectively). In each group of RV free wall image, there were also close correlations between the RV/IVS uptake ratio and both RVSP and PAMP. Our results indicate that the RV/IVS uptake ratio can be used as a parameter for the semi-quantitative estimation of right ventricular overloading.

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Ultracytochemical changes in ATPase activity of ischemic myocardial cells were studied in the dog heart by electron microscopy in the early stage of myocardial infarction and compared to the fine structural alterations in the ischemic myocardium. 1) In the normal myocardial cell, ATPase activity was observed intensely in the terminal cisternae (TC) of the sarcoplasmic reticulum (SR), and moderately on the myofilaments, in the longitudinal SR and around the gap junctions of the intercalated discs. 2) The most striking change in the ischemic myocardial cells was the reduction in the ATPase reaction product in the TC of the SR and along the gap junctions 60 min after coronary ligation, simultaneously with swelling of the TC and the appearance of mitochondrial dense deposits. The reaction product began to decrease at 30 min on the myofilaments, and for 3 to 12 hours no reaction product was observed except irreversible morphologic changes in 60 to 70% of the longitudinal SR in the ischemic subendocardial cells. 3) A decrease in ATPase activity was recognized in the early stage of myocardial ischemia simultaneously with the fine structural changes of myocardial cells and it is considered to be one of the signs of ischemic irreversibility.

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