The effects of selective cardiopulmonary receptor unloading on atrioventricular (AV) conduction were examined in 7 patients undergoing electrophysiologic testing. During -35 mmHg lower body negative pressure (LBNP) before autonomic blockade with propranolol and atropine, the AV nodal conduction time (AH interval), the effective and functional refractory periods of AV node decreased at paced cycle length, when systemic arterial and central venous pressures decreased and heart rate increased. These responseses to -35 mmHg LBNP except reductions in systemic arterial and central venous pressures disappeared after autonomic blockade. During -10 mmHg LBNP before autonomic blockade, both effective and functional refractory periods of AV node at paced cycle length decreased by 11±3% (mean±SEM) and 6±1% respectively with the reduction of central venous pressure while AH interval, systemic arterial pressure and heart rate remained unchanged. After autonomic blockade, -10 mmHg LBNP reduced central venous pressure but all the other parameters remained unchanged. These results suggest that cardiopulmonary baroreceptors participate in the reflex control of AV nodal refractoriness in humans.

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To determine the characteristic change in the Doppler hepatic venous flow velocity pattern in patients with pulmonary hypertension (PH), 21 patients with PH in sinus rhythm were examined with pulsed Doppler echocardiography. The control group included 13 subjects with chest pain syndrome and normal pulmonary arterial pressure. The hepatic vein Doppler signal was biphasic with one peak during ventricular systole (S wave) and the other in diastole (D wave). A reversed signal was recorded after contraction (A wave). The peak velocity of the A wave (Va), S wave (Vs), and D wave (Vd), the time velocity integral of these waves (Vla, Vls, and Vld), the acceleration time (t-AC), and the slope of acceleration (s-AC) in the S wave were measured. Compared with controls the PH group had a higher value of Va (26.88±10.30 vs 13.41±3.69 cm/sec; p<0.01), Vla (2.55±1.18 vs 1.20±0.34cm; p<0.01). Vla/(Vls+Vld) (0.34±0.22 vs 0.14±0.06; p<0.01), and s-AC (372±156 vs 203±103 cm/sec². p<0.01). They also had a shorter t-AC (101±32 vs 136±27 msec; p<0.01). There was a weak correlation between the reversed atrial flow and the right heart pressures (r=0.43 to 0.66). Thus, the hepatic venous flow velocity pat-tern by Doppler echocardiography is clinically useful in evaluating pulmonary hypertension.

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To clarify the histopathologic influence on diastolic function in the hypertrophied heart, we compared the echocardiographic and histopathologic findings in 9 controls, 10 patients with hypertrophic cardiomyopathy (HCM), and 8 hypertensive patients with asymmetric septal hypertrophy (HT-ASH). M-mode echocardiography was used to determine the left ventricular diastolic function. Mean diameter of myocytes, percentage of fibrosis and disarrangement were quantitatively calculated from right ventricular endomyocardial biopsy specimens. In both HT-ASH and HCM, the isovolumic relaxation time was significantly longer and the rapid filling volume tended to be smaller than in the controls. Histopathologically, the mean diameter of myocytes and percentage of myocardial interstitial fibrosis did not differ significantly between HT-ASH and HCM. However, quantitative disarrangement of myocytes in HCM was significantly greater than that in HT-ASH. Multiple regression analysis showed that the percentage of fibrosis was the most significant factor related to diastolic left ventricular dysfunction in HT-ASH, while disarrangement of myocytes was the most significant in HCM. We conclude that diastolic dysfunction in HT-ASH can be attributed to the percentage of fibrosis, and to disarrangement of myocytes in HCM.

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The left ventricular diastolic indices of the hyperthyroid (HTH) patients without cardiac disease (n=31) were compared with those of the normal controls (NC) (n=49) using echocardiography. The HTH group had a significantly shorter IIa-mitral valve opening time (IIa-MVO), and a significantly larger maximum descending rate of the left ventricular posterior wall (maxPWDR), peak E and peak A than the NC group. IIa-MVO, maxPWDR, peak E and E/A showed significant simple correlation with T₃ in the HTH group. To elucidate spurious correlation among these indices and T₃, partial correlation analysis among these indices and its influencing factors were calculated. IIa-MVO, maxPWDR and peak E showed significant partial correlation coefficients with T₃, but peak E had a lesser partial correlation with T₃ than with age and left ventricular end-diastolic volume. Fourteen of the hyperthyroid patients were reexamined after antithyroid treatment. Their diastolic indices were found to be normalized compared with pre-treatment values and showed no significant difference with those of NC group. Augmented myocardial relaxation in patients with hyperthyroidism correlated with the thyroid hormone level, and IIa-MVO and maxPWDR were more effective indices of left ventricular myocardial relaxation than peak E and E/A in hyperthyroidism.

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Twenty-one patients were successfully resuscitated from cardiac arrest. Electrocardiograms (ECG) during cardiac arrest were recorded in 14 patients with ventricular fibrillation in 7, ventricular tachycardia in 4, cardiac standstill in three, Torsade de Points in one and atrial fibrillation with rapid ventricular response in 1. Thirteen patients (group I) had structural heart disease or primary ECG abnormality and 8 patients (group II) had no apparent heart disease. Electrophysiologic study (EPS) was performed in 12 patients of group I and 5 of group II. In group I, ventricular tachycardia was induced in 7, and His-ventricular conduction disturbance was demonstrated in 2, and 2 patients with Wolff-Parkinson-White (WPW) syndrome had an effective refractory period of the antegrade accessory pathway <250 msec. No patients in group II showed abnormal EPS findings. Spasm provocation test was performed in 8 patients (2 in group I and 6 in group II). Coronary spasm was induced In 5 patients (1 in group I and 4 in group II). Two patients in group 11 had positive results of upright-tilt testing. During the follow-up period, 2 patients died suddenly in group I and 1 patient whose cause of cardiac arrest was unknown had a recurrence of cardiac arrest. In group II, all patients whose etiology could be demonstrated by serial examinations had good prognosis. In conclusion. EPS is useful in evaluation of the cause of cardiac arrest especially when patients have structural heart disease, and coronary spasm may be involved in patients with cardiac arrest without apparent heart disease.

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Thirty-eight consecutive patients with Kawasaki disease (18 patients with normal coronary artery and 20 with coronary artery lesions) were studied in order to find the incidence of myocardial abnormalities and the influence of the myocardial damage on the regional wall motion of the left ventricle in patients with Kawasaki disease with or without coronary artery lesion. Abnormal regional wall motion of the left ventricle was found in 28% of the patients with normal coronary artery (NCA) and in 55% of those with coronary artery lesions (CAL). Hypertrophy of myocytes, degeneration of myocytes and disarray were found frequently in the patients with CAL. The histopathology of endomyocardial biopsy taken from patients more than 3 years after disease onset and less than 3 years after onset were compared. Histopathologic abnormalities were found even in the biopsies taken more than 3 years after onset, especially from patients with coronary artery lesions, although the incidence of abnormalities was less frequent. We consider that repeat endomyocardial biopsies may be necessary in the patients who have significant histopathologic changes in the first endomyocardial biopsy to clarify the natural course of myocardial abnormalities, regardless of whether or not they have CAL.

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It is generally believed that patients with dilated cardiomyopathy have a large cardiac silhouette on chest roentgenography. Contrary to this general belief, we have recently examined several patients with a dilated left ventricle (LV) on echocardiography but in whom the cardiothoracic ratio (CTR) was within normal limits. To investigate this apparent discrepancy, we evaluated the relation-ship between LV dimensions, measured on M-mode echocardiography, and CTR in 49 patients with dilated cardiomyopathy. Among these patients, 11 (22%) had a CTR less than 50% and 38 (78%) had a CTR greater than 50%. The spacial orientation (cardiac rotation) of the LV within the thorax was evaluated by magnetic resonance imaging (MRI) in 5 patients with a CTR less than 50% and in 7 patients with a CTR greater than 50%, in comparison with 7 normal controls. In each of these patients, cardiac rotation was assessed from both a transverse and a frontal MRI section. In both groups, LV end-diastolic dimension was greater than 5 cm. Transverse cardiac rotation was 32±8 degrees in patients with a CTR less than 50%. This was significantly lower than in the 7 normal controls (43±7 degrees) (p<0.05). In patients with a CTR greater than 50%, however, transverse cardiac rotation (55±5 degrees) was significantly greater than in normal controls (p<0.01). No differences in frontal cardiac rotation was observed between the 2 groups. These data indicate that a normal cardiac silhouette in patients with dilated cardiomyopathy can be explained on the basis of a counterclockwise transverse rotation of the heart with-in the thorax, and it cannot always rule out the dilatation of the LV.

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The protective effects of the PGI₂ analogue, OP-2507 against hypoxic tissue in-jury were investigated in a 60-70 min acute hemorrhagic shock model in 29 rats. To assess the metabolic recovery of mitochondria after tissue injury induced by hemorrhagic hypotension with a mean arterial pressure of 30 mmHg, we have non-invasively monitored changes in the brain tissue parameters of cyt. aa3 redox state, blood oxygenation and relative blood volume by spectrophotometry through the closed skull and intact skin. Pretreatment with 0.1 my/Kg sac. of OP-2507 at 30-40 min before induction of shock was performed on 14 rats (OP-treated group). The remaining 15 rats were used as a control (control group). There was a consistent prolongation of survival time and a significant improvement in survival rate after reinfusion of the shed blood in the OP-treated group. In this group there was a rapid and complete reoxidation of cyt. aa3 with a mean overshoot of 9+5.5% above the baseline value after reinfusion. On the other hand, in the control group the extent of reoxidation was significantly lower, with a minimal 11 ±3.2% below the base line. In order to evaluate the mechanisms involved 10 my of NaCN i.v. was administered to the living rats at 60-70 min after reinfusion of the blood in both groups. In the OP-treated group, brain Hb saturation increased up to 20% above the pre-cyanide infusion level. However in the control group there was a non-significant increase in the Hb oxygenation level. These observations indicate that in the OP-treated group oxygen consumption by mitochondria is significantly higher than that in the control group. Thus, enhanced oxygen utilization could lead to the active restoration of injured tissue by promoting oxidative phosphorylation. Under these experimental conditions the oxidative response of cyt. aa3 is concluded to correlate closely with the prognosis of shock animals in both groups. These results indicate the potential usefulness of OP-2507 in protecting the brain and other organs from oxygen insufficiency as a result of tissue ischemia and anoxia.

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The WKY/NCrj rat strain is considered to be a good animal model for hypertrophic cardiomyopathy (HCM). The purpose of this study was to examine the β-adrenergic receptor/adenylate cyclase system in the cardiac ventricles of these rats. β-adrenergic receptor density (Bmax) in the right ventricle (RV) was higher in WKY/NCrj than in Wistar rats. In contrast, Bmax in the inter-ventricular septum (IVS) was lower in WKY/NCrj than in Wistar rats. Isoproterenol-stimulated adenylate cyclase activity in cardiac ventricular slices showed that changes corresponded to the changes of Bmax in every type of studied cardiac ventricle. The intracellular adenylate cyclase pathway (GTP γ S-, NaF- and forskolin-stimulated adenylate cyclase activity in cardiac ventricular particulate fraction) did not differ between WKY/NCrj and Wistar rats in any region of the cardiac ventricles. Catecholamine levels tended to be low in the RV and to increase in the IVS of WKY/NCrj rats. Our results suggest that the activity of the β-adrenergic receptor/adenylate cyclase system varies in different cardiac ventricles of the WKY/NCrj rat model for HCM.

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Reperfusion injury in early myocardial ischemia was studied in the dog with special reference to sarcoplasmic reticulum (SR) and contraction bands. Acute myocardial ischemia (1) was induced by occlusion of the left anterior descending coronary artery (LAD) for 10, 20 and 30 min followed by reperfusion for 15 min (R). Ca^>++<-ATPase activity of SR in 10-min-R-Group was significantly reduced to 60% of control activity, but activity of 10-min-I-Group remained near the control level in subendomyocardium (Endo). ATPase activity in 30-min-I-Group diminished to 60% of control activity in Endo and it was similar for 30-min-R-Group. In ischemic myocardium, composition of major ATPase protein decreased significantly in 30-min-I-Group and similar reduction was observed in 20-min-R-Group in Endo. In morphology proportion of appearance of contraction bands in Endo was significantly increased in 20-min or longer-R-Groups. These results suggest that reperfusion injury is likely to occur when coronary artery is reflowed after 10 min of ischemia. This may be caused by increased intracellular Ca⁺⁺ at a very early stage of reperfusion period, and reperfusion injury may be induced due to acceleration in the necrotic process of the membrane system in the myocytes during ischemia.

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We investigated biochemical and structural changes in collagen in ventricles in right ventricular hypertrophy (RVH) induced by monocrotaline injection in Sprague-Dawley rats. Rats injected with monocrotaline showed significant RVH after 2 weeks compared with the vehicle-treated rats (controls). After 4 weeks, the monocrotaline-treated rats showed severe RVH with heart failure. After 2 weeks, the proportion of type III collagen in the right ventricles (RV) of the monocrotaline-treated rats increased significantly compared with controls, with a concomitant decrease in type I collagen. After 4 weeks, there was a significant increase in the proportion of type III and type V collagens in the RV. In the left ventricles (LV), the proportion of collagen types was similar in the monocrotaline-treated and control rats at 2 and 4 weeks. There was no significant difference in collagen concentration (% collagen in dry defatted tissue) between the monocrotaline-treated rats and controls at either 2 or 4 weeks in the LV and RV. Scanning electron microscopy revealed that the collagen fibrillar sheaths around the myocytes in the endomysium of the RV had thickened and formed a dense network in the monocrotaline-treated rats. In the perimysium, tendon-like collagen fibers increased and became thicker than those in the RV of controls. Giant coiled perimysial fibers were also observed in the monocrotaline-treated RV. These structural changes were more pronounced after 4 weeks of monocrotaline-treatment: Loss of myocytes was evident and was accompanied by replacement fibrosis, where dense collagen fibers aggregated parallel to the long axes of the myocytes. Our results show that biochemical and structural remodeling of collagen occurred in the RV but not in the LV during the development of RVH and heart failure, providing important clues to the pathogenesis and pathophysiology of RVH and cardiac failure in response to pressure overload.

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The purpose of this study was 1) to clarify whether augmented myocardial contraction after a brief coronary occlusion, i.e. post-ischemic hypercontraction, depends on a transient increase in coronary blood flow or preceding myocardial ischemia, and 2) to identify the role of catecholamines or calcium flux in this phenomenon. Sixteen mongrel dogs were examined in open-chest anesthetized condition. One-minute reperfusion after two-minute total coronary occlusion of the left anterior descending artery resulted in a transient increase in segment shortening. Intracoronary administration of adenosine caused hyperemia without any changes in segment shortening. Two minutes of total coronary occlusion with adenosine caused post-ischemic hypercontraction to the same degree, but without any additional hyperemia. Two minutes of partial occlusion with 75% flow reduction caused less post-ischemic hypercontraction. Post-ischemic hypercontraction did not occur after partial occlusion with 50% flow reduction, irrespective of hyperemia with adenosine during reperfusion. Propranolol or verapamil did not prevent this phenomenon. Thus, post-ischemic hypercontraction is not dependent on the transient increase in coronary blood flow, but is related to the preceding myocardial ischemia. Local release of catecholamines is not likely to be the cause. A calcium antagonist, verapamil, did not modify this phenomenon. The precise mechanism of this phenomenon is still uncertain, although some alterations in cellular hemeostasis, such as ionic changes, are likely to be the cause.

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