To elucidate a mechanism and clinical implications of chest pain and ST segment depression during exercise in patients with hypertrophic cardiomyopathy (HCM), we investigated myocardial lactate metabolism during atrial pacing in 18 patients with HCM and 7 control subjects with normal coronary arteriograms. At an average peak pacing rate of 146 beats/min, 11 patients with HCM showed the lactate extraction ratio decreasing to less than 5%, and 6 of them produced lactate, suggesting the development of myocardial ischemia. These 11 patients with abnormal lactate metabolism demonstrated ST segment depression (82%) and chest pain (73%) during pacing and also presented abnormal results (55%) on an exercise stress test. These abnormal findings were not observed in the other 7 patients who had ratios of 5% or more at peak pacing.
These observations suggest that ST segment depression and chest pain are manifestations of myocardial ischemia even in patients with HCM who have normal coronary arteriograms, and that patients with pacing induced abnormal lactate metabolism are at an increased risk of developing myocardial ischemia during exercise.

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The electrophysiological effects of intravenous administration of diphenylhydantoin (DPH) (5mg/Kg, maximum 250mg) were studied in 20 patients with sinus node dysfunction (SND). DPH shortened spontaneous cycle length (SCL) in 3 patients and lengthened it in 3. Maximum corrected sinus node recovery time (max CSRT) was prolonged in 7 patients and shortened in 3. Estimated sinoatrial conduction time was prolonged in 3 patients and shortened in 2 of 10 patients in whom this measurement was possible. However, these changes were not statistically significant. Neither were there any significant changes in PA, AH and HV intervals nor refractory periods of the atrium, the AV node and the ventricle. DPH prolonged SCL and/or max CSRT in 9 of 20 patients with SND, and it was suggested that DPH has depressant effects on the sinus node in some patients with SND. Thus, this drug should be used with caution in the treatment of ventricular arrhythmias accompanied by sinus node dysfunction.

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The aim of this study was to evaluate from hemodynamic and angiocardiographic (ACG) data the extent of left ventricular (LV) systolic dysfunction in a group of predominantly young (mean age 29 years) asymptomatic patients with severe aortic regurgitation (AR). In addition, echocardiography was performed and these data were correlated with ACG data and the value of these parameters in predicting LV dysfunction was tested. Thirty-seven patients were catheterized and 18 demonstrated LV dysfunction with an ejection fraction (EF) of <50%. These patients were classified as group A and the remaining 19 patients with EF_??_50% formed group B. While there was no difference between the 2 groups with regard to age or regurgitant fraction, the end-diastolic pressure was raised (p<0.01) and cardiac index depressed (p<0.05)significantly in group A.
Of the echocardiographic parameters, the end-systolic diameter(ESD) correlated best with the EF (coefficient of correlation=-0.7and p<0.001). In addition, the ESD was significantly higher in group A (p<0.001). When an ESD_??_48mm was used as a predictor of an EF<50% (group A) the sensitivity was 89% and the specificity 79%.
In conclusion, many young asymptomatic patients with severe AR may have severe LV systolic dysfunction and an ESD_??_48mmis a good predictor of such a subgroup.

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Pulmonary capillary 'wedge' pressures (PCWP) were measured in 20 adult cases of chronic severe anemia (CSA) before and after transfusion of 700ml of whole blood at a rate of 5ml/min. The cases were randomly divided into 2 groups of 10 cases each. Group II also received 40mg of furosemide immediately before the start of transfusion.
The majority of the cases had hemoglobin values <4g% and serum albumin values <2.5g%. Pretransfusion intracardiac pressures were normal in all the cases. Following blood transfusion (BT), appreciable rises (p<0.001) in hemoglobin and arterial and venous oxygen saturation were observed. PCWP increased significantly after BT in Group I (p<0.001). Although it decreased by 3.75% in Group II, this was not statistically significant (p<0.05).
This study implies that a blood transfusion of 700ml, given at a speed of 5ml/min in patients with CSA, results in sufficient hemodynamic stress to cause a significant rise in PCWP, and that this is completely prevented by simultaneous administration of 40mg of furosemide.

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Seventy-five elderly patients with atrial fibrillation (41 males and 34 females with a mean age of 75.6 years) were studied to evaluate the incidence of masked thyroid dysfunction. A thyrotropin (TSH)-releasing-hormone (TRH) test (intravenous injection of 250μg of synthetic TRH) was performed in the patients and 30 age matched controls without atrial fibrillation. In the controls, no abnormal TRH stimulated TSH response was observed. In the patients with atrial fibrillation, no response of TSH to TRH (hyperthyroidism) was found in 5 cases (6.6%), while hyperresponse of TSH to TRH (hypothyroidism) was found in 6 cases (8.0%). Thyroid dysfunction (hyper or hypothyroidism) was more frequently observed in the patients than in the controls (p<0.05). Two of 5 hyperthyroid patients had normal thyroid hormone levels. All patients with hyperthyroidism were treated with antithyroid drugs or ¹³¹I. Unfortunately, atrial fibrillation persisted in all but 1 case.
It is concluded that the TRH test is a useful screening test for detecting those patients with abnormal thyroid function among elderly patients with atrial fibrillation, and that hypothyroidism should be considered as a cause of atrial fibrillation in the elderly.

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Furosemide-sensitive Na-K cotransport was measured as zerotrans efflux of each ion from fresh or Na loaded erythrocytes in normotensives (n=34), essential (n=41) or secondary (n=12) hypertensives and essential (n=17) or secondary (n=5) hypotensives.
The stoichiometry of Na and K efflux was 0.9: 1 in fresh cells and 1: 1 in cells loaded with sufficient Na to give near the maximum velocity (Vmax) in a combined analysis.
There was a tendency toward a negative correlation between the Vmax of Na efflux and serum total cholesterol (p=0.09) in the whole and it was significant in normotensives (r=-0.60). Vmax of Na efflux also negatively correlated to age (p<0.01). After adjustment for age and total cholesterol level, essential hypertensives had a significantly (p<0.01) higher mean Vmax of Na efflux (0.657±0.029mM/l cells/hr) than normotensives (0.388±0.045), while essential hypotensives had a lower value (0.212±0.047) (p<0.01).
Na efflux from fresh cells adjusted for internal Na content was higher in essential hypertensives (0.173±0.018) than in normotensives (0.107±0.026) (p<0.05).
Thus, elevated cotransport was linked to essential hypertension and reduced cotransport to hypotension. Whether it is a cause or a result remains to be further investigated.

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While dynamic changes in the resistance of stenotic coronary segments were recently proposed by several investigators, the mechanisms of these changes are obscure. This study was conducted to correlate changes in coronary pressure distal to the stenosis to dynamic changes in the stenosis resistance in the canine heart. Coronary pressure distal to the stenosis was raised by either proximal aortic pressure elevation or intracoronary blood infusion distal to the stenosis. The pressure rise resulted in a significant fall in the stenosis resistance. Distal coronary pressure drop induced by phlebotomy or removal of blood from the distal coronary bed caused the reverse effects on resistance. Linear regression analysis revealed a close relationship between changes in distal coronary pressure (ΔDCP) and those in resistance of the stenotic coronary segment (ΔRL) represented by the following equation; ΔRL (dyne•cm^-5•sec×10^-3)=0.50×[ΔDCP(mmHg)]-6.0×10^-2, r=0.86, p<0.01. The results suggest that dynamic changes in stenosis resistance appear largely to be a function of the pressure changes distal to the stenosis.

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In an isolated right atrial preparation, which was cross-perfused with heparinized arterial blood from a support dog, we investigated the effects of glucagon on heart rate and systemic arterial blood pressure of the support dog and on atrial rate and contractile force of the isolated perfused atrium when glucagon was injected into the external jugular vein of the support dog or into the sinus node artery of the isolated atrial preparation. Glucagon (0.3 to 3μg/Kg i.v.) to the support dog dose-dependently induced a prominent increase in heart rate and a small increase in systemic arterial blood pressure. In the isolated, perfused atrium, marked positive chronotropic and slight, but significant, positive inotropic effects were evoked dose-dependently 1.5min after intravenous injection of glucagon. These positive effects were not altered significantly by propranolol (1mg/Kg i.v.). Direct injection of glucagon into the sinus node artery of isolated atria also induced marked positive chronotropic and small positive inotropic effects dose-dependently. CF/HR ratios, inotropic effect per chronotropic effect in isolated atria, of glucagon injected intravenously or intraarterially were less than 0.7 and they were much less than those of norepinephrine (more than 3.6). These results confirm that glucagon injected intravenously or regionally produces a prominent positive chronotropic effect and a small positive inotropic effect and suggest that glucagon may be less effective as a cardiotonic agent.

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Effects of ouabain, CaCl₂ and verapamil on the frequency-force relationship (FFR) were investigated in the isolated, blood-perfused dog atrial muscle preparation. When ouabain (3 and 10μg) or CaCl₂ (0.5, 1 and 2mg/min) was given into the sinus node artery, the contractile force of the atrial muscle, driven at a constant pacing rate of 2Hz, increased dose-dependently. Verapamil (1 and 3μg) decreased the atrial contractile force dose-dependently. When the pacing rate was changed from 2 to 3.5Hz, the atrial contractile force increased in parallel with the pacing rate (positive FFR). After treatment with ouabain and verapamil, the contractile force declined at higher frequencies (negative FFR). The verapamilinduced negative FFR was much steeper than the ouabain-induced relationship. An infusion of CaCl₂ modified the FFR such that higher doses of CaCl₂ elicited a negative FFR only at higher pacing rates. However, the CaCl₂-induced FFR did not differ from the negative FFR induced by verapamil or ouabain. It was demonstrated that the cardiotonic agents ouabain and CaCl₂, as well as verapamil induced negative FFR in the isolated dog heart.

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In anesthetized dogs, an intravenous injection of nipradilol produced a long lasting fall in mean arterial blood pressure which was accompanied by transient decreases in peripheral vascular resistance and sustained decreases in heart rate, cardiac output and left ventricular (LV) dP/dt. LV end-diastolic pressure (LVEDP) was not changed while LV diameters and central venous pressure were slightly increased. Under propranolol pretreatment conditions, nipradilol no longer affected the heart rate, but the drug still induced a transient reduction in peripheral vascular resistance, and sustained decreases in arterial blood pressure and cardiac output. Furthermore, indicators of LV preload (LVEDP, LV enddiastolic diameter and central venous pressure) were significantly reduced, suggesting a direct dilating action of nipradilol on capacitance vessels. In intact conscious dogs, nipradilol caused a sustained reduction in LVEDP, while propranolol increased LVEDP. After administration of nipradilol, coronary blood flow in anesthetized dogs decreased in association with diminished myocardial oxygen consumption, and large coronary vessel resistance also decreased. Nipradilol competitively antagonized the isoproterenolinduced positive chronotropic response (DR10: 0.04mg/Kg, i.v.) and the phenylephrine-induced vasopressor response (DR10: 3.95mg/Kg, i.v.). In conclusion, nipradilol, in contrast to propranolol, possesses the properties to decrease arterial blood pressure, LV preload and large coronary vessel resistance through its dilating action on arterial and venous vessels. It is proposed that nipradilol may be beneficial for the treatment of hypertension and coronary heart disease.

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The coronary vasoconstrictor effects of neuropeptide Y (NPY) were confirmed in anesthetized closed-chest dogs. This NPY-induced vasoconstriction was not affected by alpha- or betaadrenergic blockers and nifedipine given into the perfusion circuit abolished the constriction. After intracoronary nifedipine administration, coronary flow exceeded the control level within 60sec, then returned to a level between the control value before NPY and the lowest value elicited by NPY after 10min. When nifedipine was given systemically before NPY, the peak response to NPY was attenuated, suggesting a preventive effect of nifedipine on the NPY-induced coronary vasoconstriction.
Since NPY is found in the hearts of many species, including man, NPY may cause coronary vasospasms. An effect on NPY-induced coronary vasoconstriction of nifedipine may be compatible with the beneficial clinical effects of this drug.

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The effects of intracoronary (i.c.) and intravenous (i.v.) or intraventricular (i.vt.) urokinase (UK) administration were studied in a canine experimental model in which a coronary thrombus was produced by a modified electrical stimulation method. The success rate of coronary thrombolysis was 77% (17/22) with i.c. administration of 4, 000U/Kg of UK. Either i.v. or i.vt. UK administration of less than 24, 000U/Kg induced thrombolysis in 25% (2/8), while i.v. administration of more than 25, 000U/Kg resulted in a success rate of 64% (7/11) with a fibrinogen reduction from 313±63mg/dl to 116±34mg/dl.

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A case with an exceptional form of congenitally bicuspid aortic valve is described. A fibrous strand connected to the supra-aortic ridge supported the conjoined cusp, and severe pure aortic regurgitation was present although the fibrous strand remained intact. Aortic valve replacement was successfully performed.

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A case with massive lipomatous infiltration to the left ventricle is reported. An intracardiac tumor was suspected on the results of echocardiography, computed tomography, thallium scintigraphy and left ventriculography. This is the first case which was diagnosed in vivo and successfully resected.

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