Tricuspid annular plane systolic excursion and pulmonary arterial systolic pressure relationship in heart failure: an index of right ventricular contractile function and prognosis.

Echo-derived pulmonary arterial systolic pressure (PASP) and right ventricular (RV) tricuspid annular plane systolic excursion (TAPSE; from the end of diastole to end-systole) are of basic relevance in the clinical follow-up of heart failure (HF) patients, carrying two- to threefold increase in cardiac risk when increased and reduced, respectively. We hypothesized that the relationship between TAPSE (longitudinal RV fiber shortening) and PASP (force generated by the RV) provides an index of in vivo RV length-force relationship, with their ratio better disclosing prognosis. Two hundred ninety-three HF patients with reduced (HFrEF, n = 247) or with preserved left ventricular (LV) ejection fraction (HFpEF, n = 46) underwent echo-Doppler studies and N-terminal pro-brain-type natriuretic peptide assessment and were tracked for adverse events. The median follow-up duration was 20.8 mo. TAPSE vs. PASP relationship showed a downward regression line shift in nonsurvivors who were more frequently presenting with higher PASP and lower TAPSE. HFrEF and HFpEF patients exhibited a similar distribution along the regression line. Given the TAPSE, PASP, and TAPSE-to-PASP ratio (TAPSE/PASP) collinearity, separate Cox regression and Kaplan-Meier analyses were performed: one with TAPSE and PASP as individual measures, and the other combining them in ratio form. Hazard ratios for variables retained in the multivariate regression were as follows: TAPSE/PASP

Carotid body chemoceptors: physiological role in buffering fall in blood pressure during sleep.

In cats whose aortic nerves were severed subsequent deafferentation of the carotid body chemoceptors (the carotid sinus baroceptors remaining intact) did not change arterial pressure during wakefulness or light sleep, but the falls in pressure during deep sleep were markedly exaggerated. Subsequent baroceptive denervation did not modify the hypotensive effect.

Impaired brachial artery endothelial flow-mediated dilation and orthostatic stress in hemodialysis patients.

PURPOSE: Chronic kidney disease (CKD) is associated with an impaired endothelial function, which may contribute to cardiovascular events. Whether impairment in endothelial function is involved in the circulatory response to orthostatic stress is unknown. We assessed endothelial function via brachial artery flow-mediated dilation (BAFMD), an index of endothelial-dependent vasodilation. METHODS: We measured changes in brachial artery diameter (BAD) and blood flow by Doppler ultrasound in 35 CKD patients on hemodialysis, 37 young healthy controls (HC) and 50 non-uremic matched controls (MC), in the supine position and after 60 degrees head-up tilting (HUT). RESULTS: In the supine position, endothelial flow-mediated BAD was significantly increased in HC (p<0.001) and MC (p<0.01) while no significant changes were detected in CKD. Mean percent blood flow changes were HC+323.5%, MC+195.1% and CKD+158.8% (HC vs. CKD p<0.001; HC vs. MC p<0.001; MC vs. CKD p=0.04). Similarly, during HUT mean BAD and blood flow increases were significantly impaired in CKD patients. CONCLUSION: In CKD patients, an impaired response in the physiologic vascular reactivity, suggesting endothelial dysfunction, was found in the supine position and after orthostasis by BAFMD. Our results are in favor of a possible adjunctive role of uremia in the abnormal brachial artery response.

Sildenafil reduces L-NAME-induced severe hypertension and worsening of myocardial ischaemia-reperfusion damage in the rat.

BACKGROUND AND PURPOSE: Phosphodiesterase-5 inhibitors are beneficial in pulmonary hypertension and congestive heart failure, the two conditions associated with coronary heart disease and ischaemia. We investigated whether sildenafil counteracts the cardiovascular alterations induced by N -nitro-L-arginine methyl ester (L-NAME) in the rat. EXPERIMENTAL APPROACH: Sildenafil was given orally to rats at doses of 0.37, 0.75 or 1.5 mg kg-1day-1 for four weeks, either alone or with L-NAME (35-40 mg kg-1 day-1 in the drinking water). Systolic blood pressure and urinary parameters (6-keto-prostaglandin F1alpha, thromboxane B2, 8-isoprostane-prostaglandin F2 and nitrite/nitrate) were measured in conscious rats. Isolated hearts were subjected to low flow ischaemia-reperfusion, and myocardial levels of guanosine 3', 5'cyclic monophosphate (cGMP) were determined. Endothelial vascular dysfunction was examined in aortic rings. KEY RESULTS: Sildenafil dose-dependently prevented the rise in systolic blood pressure in L-NAME-treated rats. This activity was associated with a normalization of urinary 8-isoprostane-prostaglandin F2alpha and other biochemical parameters. In perfused hearts, the post-ischaemic ventricular dysfunction was worse in preparations from L-NAME-treated rats than in controls. Sildenafil dose-dependently reduced this effect, and creatine kinase and lactate dehydrogenase release were lower too. cGMP levels, which were low in myocardial tissue from L-NAME-treated rats, were restored by sildenafil. In noradrenaline-precontracted aortic rings from L-NAME-treated rats acetylcholine lost its vasorelaxant effect, and sildenafil restored it. CONCLUSION AND IMPLICATIONS: In a rat model of chronic nitric oxide deprivation, where hypertension and aggravation of post-ischaemic ventricular dysfunction are associated with loss of vascular endothelium-relaxant function, sildenafil provided significant cardiovascular protection, primarily by maintaining tissue cGMP levels.

Modulation of alveolar-capillary sodium handling as a mechanism of protection of gas transfer by enalapril, and not by losartan, in chronic heart failure.

OBJECTIVES: We sought to compare the protective efficacy of enalapril and losartan on lung diffusion in chronic heart failure (CHF). BACKGROUND: In CHF, hydrostatic overload causes disruption of the alveolar-capillary membrane and depression of carbon monoxide diffusion (DCO); enalapril improves DCO through mechanisms still undefined; and saline infusion in the pulmonary circulation worsens DCO, putatively because of an upregulated sodium transport to the alveolar interstitium. We investigated whether enalapril modulates sodium handling and whether losartan shares the same properties. METHODS: In 29 patients with CHF, DCO, its membrane diffusion subcomponent (DM) and right atrial and pulmonary wedge pressures were monitored during saline infusion, in the control condition, during enalapril therapy (20 mg/day) for two weeks and after crossover to losartan (50 mg/day) for two weeks (first 20 patients), or after the combination of enalapril with aspirin (325 mg/day) for one week (last 9 patients). RESULTS: Saline, 150 ml, lowered DCO (-7.9%; p < 0.01) and DM (-9.9%; p < 0.01) without hydrostatic variations. Responses to 750 ml of saline were qualitatively similar. After treatment with enalapril, baseline DCO (p < 0.01) and DM (p < 0.01) were augmented; after sodium loading, the percent reductions of DCO (p < 0.01) and DM (p < 0.01) were comparable to those before it, resulting in higher absolute values. This suggests that the greater the gas conductance improvement with enalapril, the lower the impedance with saline. Losartan was ineffective on gas transfer at rest and under salt challenge. Aspirin counteracted the benefits of enalapril. CONCLUSIONS: In CHF, enalapril protects lung diffusion, possibly through a prostaglandin-mediated modulation of sodium overfiltration to the alveolar interstitium; losartan does not share this ability.

How the left and right sides of the heart, as well as pulmonary venous drainage, adapt to an increasing degree of head-up tilting in hypertrophic cardiomyopathy: differences from the normal heart.

OBJECTIVES: We aimed to assess the differences in the adaptive response of patients with hypertrophic cardiomyopathy (HCM) compared with normal subjects, as well as any association with increased susceptibility to the test. BACKGROUND: Diastolic function contributes importantly in the adaptation of the normal heart to head-up tilting. This mechanism may be disturbed by an impaired relaxation in HCM. METHODS: Twenty-one male patients with HCM (46 +/- 6 years old) and 22 healthy men (44 +/- 8 years) were studied using Doppler echocardiography after 1 and 10 min of head-up tilting at 20 degrees, 40 degrees and 60 degrees. RESULTS: In control subjects, tilting was associated with 1) a predominance of diastolic pulmonary venous flow and early left ventricular (LV) filling (atrium functioning as an open conduit); 2) right ventricular (RV) shrinkage; and 3) no LV dimensional variations. In patients with HCM, tilting was associated with 1) a prevalence of systolic pulmonary venous flow (atrium functioning as a reservoir in which filling depends on atrial relaxation and compliance) and late diastolic transmitral flow (atrium working as a booster pump); 2) LV shrinkage; and 3) no RV dimension variations. These mechanisms did not prevent stroke volume (SV) from decreasing at 40 degrees and 60 degrees in both groups. Because of a lower increase in heart rate (HR), a reduction in cardiac output (CO) was greater in patients with HCM. The responses were similar after 1 and 10 min of tilting in control subjects, whereas in patients, blood pressure (BP), SV and LV dimension fell more after 10 min. CONCLUSIONS: Adaptation of the normal heart to tilting is based on a ventricular interaction and LV diastolic properties; HCM relies on left atrial diastolic and systolic functions. An inadequate HR reaction to a fall in BP and SV in HCM (depressed reflexogenic activity) contributes to making CO more vulnerable by greater and more prolonged displacements.

Left atrial function and ventricular filling in hypertensive patients with paroxysmal atrial fibrillation.

OBJECTIVES: We evaluated left atrial dimensions and function, as well as left ventricular structure and filling, in hypertensive patients with paroxysmal atrial fibrillation. BACKGROUND: In hypertensive patients, left atrial dilation and enhanced volume transport may facilitate arrhythmias. METHODS: Left ventricular two-dimensional and M-mode echocardiograms and pulsed Doppler echocardiography of transmitral flow were performed in 17 consecutive primary hypertensive patients with paroxysmal atrial fibrillation (group EHf) and in 34 patients with high blood pressure without this arrhythmia (group EH). Seventeen normal subjects (group N) were also investigated. Groups were matched for age and gender. RESULTS: The EH and EHf groups had similar systolic arterial pressures ([mean +/- SD] group EH 185 +/- 27, group EHf 173 +/- 25 mm Hg, p = NS) and left ventricular mass index (group EH 154 +/- 55, group EHf 131 +/- 57.8 g/m2, p = NS), and their M-mode left ventricular systolic wall stress and fractional shortening were comparable to those of normal subjects. M-mode left atrial maximal (group N 37.8 +/- 6, group EH 37.9 +/- 4.6, group EHf 44.6 +/- 6.7 mm, p < 0.05 for group EHf vs. groups N and EH) and minimal diameters and the diameter preceding atrial contraction (group N 31 +/- 3.6, group EH 34.5 +/- 5, group EHf 40.4 +/- 6.9 mm, p < 0.001 for group EHf vs. group N; p < 0.05 for group EHf vs. group EH) were greater in group EHf than in group EH and group N subjects, whereas only the latter diameter was increased in group EH (p < 0.05 vs. group N), so that left atrial fractional shortening was higher than normal only in group EH (group N 10.8 +/- 4.4%, group EH 14.6 +/- 5.5%, group EHf 9.3 +/- 5.3%; group EH vs. group N, p < 0.05; group EHf vs. group EH, p < 0.05). The pulsed Doppler ratio of early to late transmitral flow rates (E and A wave velocity/time integrals x mitral annulus area) was lower than normal in group EH (group N 2.9 +/- 2.2, group EH 1.75 +/- 0.8, group EHf 2.8 +/- 0.8; group EH vs. group N, p < 0.05; group EHf vs. group EH, p < 0.001; group EHf vs. group N, p = NS) and was "normalized" in group EHf, early flow being increased in this group (group N 42 +/- 13, group EH 39 +/- 29, group EHf 60 +/- 17 ml; group EHf vs. group N, p < 0.05; group EHf vs. group EH, p < 0.05). CONCLUSIONS: These results suggest that the occurrence of paroxysmal atrial fibrillation in hypertension is associated with enlargement of the left atrium, depression of its contractile function and "normalization" of the pattern of left ventricular filling and is independent of left ventricular hypertrophy and systolic wall stress. The mechanisms linking these variables remain undefined.

How the two sides of the heart adapt to graded impedance to venous return with head-up tilting.

OBJECTIVES: The study sought to probe whether the adaptation of the right ventricle to reduced preload may influence that of the left ventricle (interdependence) and whether and how this mechanism contributes to maintain an adequate pump function. BACKGROUND: A study like this requires that subjects be normal, restraint of venous return be gradual, systolic function and diastolic filling and dimensions of either ventricle be monitored. METHODS: Of 30 healthy men (mean [+/- SD] age 35 +/- 7 years) studied with Doppler echocardiography, 20 were studied in the supine position and after 20 degrees, 40 degrees and 60 degrees tilting for 10 min; the remaining 10 subjects were also studied at the same levels of tilting for 45 min. RESULTS: At 20 degrees, heart rate, blood pressure and stroke volume were steady; the diastolic right ventricular area was reduced (p < 0.001); and the end-diastolic dimension of the left ventricle did not vary. Tilting at 40 degrees and 60 degrees increased heart rate and diastolic pressure, decreased systolic pressure and stroke volume and reduced the diastolic dimensions of both ventricles. At any tilting level, right and left peak early inflow velocities (E) were decreased, peak late velocities (A) were unchanged, and E/A ratios were reduced, suggesting that the atrial-ventricular pressure difference was diminished bilaterally and that the atrial contribution to ventricular filling was maintained. Tachycardia at 40 degrees and 60 degrees tilting was not associated with enhancement of left ventricular fiber fractional shortening or mean velocity of shortening for any corresponding end-systolic wall stress; changes in heart rate also did not correlate with those in fiber fractional shortening and velocity of shortening. The adaptive responses to the same degrees of tilting for a duration of 45 min were comparable to those at 10 min. CONCLUSIONS: With moderate restraint of venous return, the left ventricle maintains filling and output in response to a reduction in right ventricular diastolic volume, which increases left ventricular compliance (interdependence), and to the pulmonary blood reservoir, which compensates for an immediate decrease in right ventricular stroke volume. The decreased lung blood volume would facilitate right ventricular ejection, resulting in a normal stroke output despite the reduced preload. Thus, mechanical adjustments fully compensate for moderate reduction of venous return. A more severe reduction requires chronotropic support for the maintenance of cardiac output. With prolongation of tilting time to 45 min, adaptive mechanisms do not become exhausted in normal persons.

Pulmonary vascular supersensitivity to catecholamines in systemic high blood pressure.

Pulmonary pressure and arteriolar resistance are elevated in uncomplicated primary systemic hypertension. This study was carried out in 16 men with this form of hypertension and in 9 healthy men to compare 1) their pulmonary vascular reactivity to endogenous catecholamines released during mental arithmetic and cold pressor tests, and 2) the dose-response relation to exogenous epinephrine and norepinephrine. Arithmetic and cold pressor tests were associated, respectively, with a predominant increase in plasma epinephrine and norepinephrine concentration; changes were significantly greater in hypertensive men. During the two tests, pulmonary arteriolar resistance in the normotensive group was reduced by 13% and augmented by 7% of baseline, respectively, whereas it was raised by 31 and 70%, respectively, in the hypertensive group. In normal subjects, the dose (microgram)-response (delta dynes) relation to epinephrine was 1 = -4, 2 = -9, 3 = -9 and 4 = -10; to norepinephrine it was 2 = +3, 4 = +6, 6 = +7 and 8 = +7. In hypertensive patients, the respective relations were 1 = +18, 2 = +44, 3 = +59 and 4 = +77; and 2 = +39, 4 = +54, 6 = +76 and 8 = +98. Group differences were highly significant. In each of these circumstances, the driving pressure across the lungs was significantly augmented in the hypertensive but not the normotensive group. Both epinephrine and norepinephrine have a vasoconstrictor influence on the lesser circulation as a consequence of vascular overreactivity. The opposite changes in resistance between normotensive and hypertensive subjects produced by epinephrine suggest that a constrictor vascular supersensitivity becomes active in the pulmonary circuit with the development of systemic high blood pressure.

Lack of improvement of lung diffusing capacity following fluid withdrawal by ultrafiltration in chronic heart failure.

OBJECTIVES: We sought to investigate the possibility that lung diffusing capacity reduction observed in chronic heart failure is reversible in the short term. BACKGROUND: Mechanical properties of the lung usually ameliorate with antifailure treatment including drugs, ultrafiltration and heart transplantation, whereas lung diffusion rarely improves. METHODS: We studied the mechanical properties of the lung (pulmonary function tests with determination of alveolar volume, extravascular lung fluids and lung tissue), lung diffusion for carbon monoxide (DLco), including membrane diffusing capacity (Dm), pulmonary capillary blood volume (Vc) and pulmonary hemodynamics, in 28 patients with stable chronic heart failure, before a single session of extracorporeal ultrafiltration (3,973 +/- 2200 ml) and four days thereafter. Lung mechanics and diffusion were also evaluated in 18 normal subjects. RESULTS: Vital capacity, forced expiratory volume (1 s) and maximal voluntary ventilation were lower in patients when compared with normal subjects, and increased after ultrafiltration from 2.1 +/- 0.7 to 2.5 +/- 0.7(1)*, 1.7 +/- 0.5 to 2.0 +/- 0.6(1)* and 67 +/- 25 to 79 +/- 26 (1/min)*, respectively (* p < 0.02 vs. pre-ultrafiltration). Post-ultrafiltration alveolar volume was augmented, while lung tissue, body weight (approximately 6 kg), chest X-ray extravascular lung water score and pulmonary vascular pressure were reduced. Heart dimensions (echocardiography) remained unchanged. DLco, Dm and Vc were 29.0 +/- 5.0 ml/min/mm Hg, 47.0 +/- 11.0 ml/min/mm Hg, 102 +/- 20 ml in normal subjects and 17.1 +/- 4.0#, 24.1 +/- 6.5#, 113 +/- 38 and 17.0 +/- 5.0#, 24.8 +/- 7.9#, 100 +/- 39 in patients before and after ultrafiltration, respectively (# = p < 0.01 vs. controls). CONCLUSIONS: In chronic heart failure, ultrafiltration improves volumes and mechanical properties of the lung by reducing lung fluids. Diffusion is unaffected by ultrafiltration, suggesting that, in chronic heart failure, the alveolar-capillary membrane abnormalities are fluid-independent.

Isolated ultrafiltration in moderate congestive heart failure.

OBJECTIVES: The aim of this study was to evaluate whether ultrafiltration is beneficial in patients with moderate congestive heart failure. BACKGROUND: Ultrafiltration is beneficial in patients with severe congestive heart failure. METHODS: We studied 36 patients in New York Heart Association functional classes II and III in stable clinical condition. Eighteen patients (group A) were randomly selected and underwent a single session of ultrafiltration (venovenous bypass, mean [+/- SEM] ultrafiltrate 1,880 +/- 174 ml, approximately 600 ml/h) and 18 (group B) served as control subjects. RESULTS: Two patients in group A and three in group B did not complete the 6-month follow-up study. In group A, soon after ultrafiltration there were significant reductions in right atrial pressure (from 8 +/- 1 to 3.4 +/- 0.7 mm Hg, pulmonary wedge pressure (from 18 +/- 2.5 to 10 +/- 1.9 mm Hg) and cardiac index (from 2.8 +/- 0.2 to 2.3 +/- 0.2 liters/min). During the follow-up period, lung function improved, extravascular lung water (X-ray score) decreased and peak oxygen consumption (ml/min per kg) increased significantly from 15.5 +/- 1 (day -1) to 17.6 +/- 0.9 (day 4), to 17.8 +/- 0.9 (day 30), to 18.9 +/- 1 (day 90) and to 19.1 +/- 1 (day 180). Oxygen consumption at anaerobic threshold (ml/min per kg) also increased significantly from 11.6 +/- 0.8 (day -1) to 13 +/- 0.7 (day 4), to 13.7 +/- 0.5 (day 30), to 15.5 +/- 0.8 (day 90) and to 15.2 +/- 0.8 (day 180). These changes were associated with increased ventilation, tidal volume and dead space/tidal volume ratio at peak exercise. The improvement in exercise performance was associated with a decrease in norepinephrine at rest, a downward shift of norepinephrine kinetics at submaximal exercise and an increase in norepinephrine during orthostatic tilt. None of these changes were recorded in group B. CONCLUSIONS: In patients with moderate congestive heart failure, ultrafiltration reduces the severity of the syndrome.

Pulmonary vasomotor responses to neural activation in man.

Passive adaptation to changes in flow is an established mechanism of regulation of pulmonary vasomotility. The role of the autonomic nervous system is not well defined in man. To separate the neural from the mechanical component (variation in flow) the venous return and the lung blood flow of six normal men (while undergoing haemodynamic diagnostic procedures) were impeded by a balloon tipped catheter placed in the inferior vena cava. Mental arithmetic and cold pressor tests were used as sympathetic activators. When the venous return was impeded cardiac output was reduced by a mean of 540 ml compared with baseline. During the arithmetic test the rise in cardiac output fell from 2140 ml when venous return was unimpeded to 890 ml when venous return was impeded. This stimulus changed from being a slight pulmonary vasodilator to being an unequivocal vasoconstrictor. Cold stimulation had little effect on cardiac output and caused an increase in pulmonary arteriolar resistance. This effect was more than doubled when flow through the lungs was impeded. These observations suggest that a neural regulation of the pulmonary circulation exists in man, which is disclosed (arithmetic test) or potentiated (cold pressor test) when the influence of mechanical factors is prevented or reduced.

Pulmonary vasoconstrictor overreactivity in borderline systemic hypertension.

Raised vascular pressure and resistance and vasoconstrictor overreactivity to adrenergic stimulation are hallmarks of the pulmonary circulation in sustained primary hypertension. The aim of this study was to investigate the reasons for these disorders. In 10 males with borderline systemic hypertension, pulmonary haemodynamic variables were similar to those of an age matched group of eight normotensive subjects. In normotension, arithmetic and cold pressor tests (sympathetic activators) caused slight vasodilatation and vasoconstriction, respectively. In hypertension both tests showed an obvious vasoconstrictor effect. Restriction of blood flow through the lungs by distension of a balloon in the inferior vena cava is known to increase pulmonary vasoconstrictor reactivity in normal man. As a result of this manoeuvre, pulmonary pressure fell in the normotensive controls without variation in pulmonary vascular resistance, whereas in the hypertensive group there was an increase in resistance and the pressure did not change. In normotensive subjects with caval balloon, the sympathetic activating stimuli both became constrictor and caused vascular resistance to rise to the levels attained in the hypertensive patients during adrenergic stimulation in the absence of obstruction to venous return. In the hypertensives, these stimuli were not able to enhance the pulmonary vascular resistance further. This shows that in these patients maximal vasoconstriction was already achieved through the simple restraint of blood flow with vena caval obstruction. We suggest that in the early phases of systemic hypertension lung vessels are hypercontractile so that they overreact to hypoperfusion or to sympathetic stimulation, even before there is a stable rise in pressure and resistance.

Stress-induced and sympathetically-mediated electrocardiographic and circulatory variations in the primary hyperkinetic heart syndrome.

As shown by the inotropic changes, the sympathetic discharge on the heart, is selectit syndrome. In the steady state the electrocardiogram shows flat, diphasic, or "tucked' T waves. Mental stimulation or isoproterenol, and, respectively, pain or beta blockade induce changes of the repolarization phase divergent from steady state. The former causes ST depression and deep T-wave inversion and the latter fully normalizes the repolarization phase. It is concluded that the electrical activity of the heart is directly influenced by the adrenergic drive in this disorder, and that different stressful factors can alter the repolarization phase in opposite ways in relation to the influence of the stimulus on the cardiac sympathetic tone.

Circulatory and renin responses in man to unilateral reduction of the renal perfusion pressure.

This study is concerned with the mechanisms of human renovascular hypertension. Unilateral partial occlusion of a renal artery was accomplished using a balloon-tipped catheter for occlusive angiography in seven normotensive and 17 primary hypertensive subjects. The renin and circulatory responses were studied during a 60 min reduction of the renal perfusion pressure (RPP) by 50% of control. This stimulus was considered to be safe and strong enough to produce a three to four-fold rise in plasma renin activity. It was observed that: a) systemic (arterial) renin was significantly raised at 5 min, reached a peak at 15 min and continued to be significantly higher than the baseline until the occlusion was removed; b) venous renin and venous arterial difference on the occluded side became elevated after the stimulus and remained so for the duration of the occlusion; c) renin release from the contralateral kidney became partially inhibited; d) in no case did systemic arterial pressure, heart rate or cardiac output change during the studies; e) renin and circulatory patterns were similar in normotensive and hypertensive subjects. It is concluded that in humans unilateral RPP reduction duplicates the renin pattern of the Goldblatt kidney, but does not duplicate the circulatory response. This evidence applies to a 1 h renal artery occlusion and does not exclude the possibility that renin may have a role in a rise in blood pressure following renal artery stenosis of longer duration.

Cardiac hypertrophy in hypertension. Repolarization abnormalities elicited by rapid lowering of pressure.

In hypertension, coronary flow is augmented and oxygen balance is adequate despite an increase in coronary resistance. For the maintenance of flow in the presence of and after regression of ventricular hypertrophy, the ratio of pressure and ventricular mass must remain normal. Coronary reserve would be altered if treatment normalized pressure but not ventricular mass or if pressure were lowered too fast. We investigated 42 patients with primary hypertension. In 28 (Group I) left ventricular mass index (by ultrasound) was within the mean value +2 SD (96 + 38 g/m2) of 145 controls and exceeded these values in the remaining 14 patients (Group 2). The diastolic pressure was lowered rapidly to between 85 and 90 mm Hg with two potent vasodilators, nifedipine (sublingually) and nitroprusside, while a 12-lead electrocardiogram was recorded continuously. During both tests, seven patients in Group 2 (responders) showed inversion of normal T waves, in lead I, aVL, and V3-6. These changes waxed and waned in parallel with the pressure fall and recovery and were not attributable to alterations in adrenergic tone, conduction disturbances, variations, or group differences in the QRS axis, QTc interval, heart rate, left ventricular fractional shortening, wall stress, rate of dimension increase in early diastole, or isovolumic relaxation. A ""steal phenomenon'' or passive collapse in compliant coronary lesions during vasodilatation seems unlikely; in fact, patients were free from coronary symptoms, and the electrocardiographic alterations occurred only in seven patients in Group 2, who had a greater left ventricular mass index and required a larger pressure drop to return the diastolic pressure to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of hypertension with calcium antagonists. Review.

Calcium channel blockers have a selective action on the cardiovascular system. They reduce the energy requirement of the heart, reduce vascular smooth muscle tone, and increase systemic blood flow. Vasodilatation occurs in both the systemic and the pulmonary systems to an extent proportional to the baseline level of vascular resistance, and results in reduction of blood pressure when it is elevated. Thus, these blockers are useful in patients with high blood pressure. Clinical experience of calcium channel blockers in hypertension is so far confined almost exclusively to verapamil and nifedipine. This article reviews the advantages and limitations of these two compounds, their acute hemodynamic effects in hypertensive subjects, and their use in the treatment of hypertensive emergencies, hypertensive encephalopathy, and pheochromocytoma, and as ventricular afterload reducing agents in hypertensive left ventricular failure. Similarities in the effects of nifedipine on systemic and pulmonary vascular tone are presented as evidence that altered intracellular Ca++ concentration is involved in the vasoconstriction seen in both systems in systemic high blood pressure. They also provide support for the hypothesis that inappropriate Ca++ handling may be involved in maintaining elevated blood pressure in human hypertension.