Cardiac function and peripheral circulatory adjustments in patients with acute myocardial infarction. Observations during the early stage of AMI

Since little is known concerning the effect of different types of cardiac dysfunction on the peripheral circulation in acute myocardial infarction, cardiac and peripheral circulatory hemodynamics were measured simultaneously and sequentially in the Coronary Care Unit in 40 patients with acute myocardial infarction (AMI) using a Swan-Ganz catheter and venous occlusion plethysmography. Patients were classified by clinical assessment (Killip) and into four hemodynamic subsets (HS) according to pulmonary capillary wedge pressure (PCWP) and cardiac index (CI) measures obtained by invasive central hemodynamic monitoring (Forrester): uncomplicated AMI, HS-I (PCWP less than or equal to 18 mmHg, CI greater than 2.2 L/min/m2) 15; pulmonary congestion, HS-II (PCWP greater than 18 mmHg, CI greater than 2.2 L/min/m2) 15; peripheral hypoperfusion, HS-III (PCWP less than or equal to 18 mmHg, CI less than or equal to 2.2 L/min/m2) 4; cardiogenic shock, HS-IV (PCWP greater than 18 mmHg, CI less than or equal to 2.2 L/min/m2) 6. Measurements taken within 48 hours after the onset of AMI showed significantly lower calf blood flow (p less than 0.05) and calf venous capacitance (p less than 0.01) and higher calf vascular resistance (p less than 0.05) in all AMI classifications compared to 10 normal subjects. In uncomplicated AMI group (Killip I and HS-I) calf blood flow and venous capacitance were significantly reduced while calf vascular resistance remained unchanged from normal. In AMI complicated by pulmonary congestion (Killip II and HS-II), in addition to reduced calf venous capacitance, calf blood flow was further significantly reduced (p less than 0.05) due, in part, to a rise in calf vascular resistance (p less than 0.05). In AMI complicated by severe heart failure and shock (Killip III, VI and HS-IV), mean changes in the periphery were not statistically different from those seen in patients with pulmonary congestion alone. In patients with AMI complicated by poor peripheral perfusion (HS-III), the peripheral changes did not show significant differences from those seen in uncomplicated AMI (HS-I). Significant correlations were found between calf blood flow and PCWP (r = -0.37, p less than 0.05) and CVP (r = -0.31, p less than 0.05); calf vascular resistance and PCWP (r = +0.36, p less than 0.05) and systemic vascular resistance (r = +0.43, p less than 0.01). Sequential daily peripheral hemodynamic changes in 14 H-I patients not requiring specific therapy showed that calf blood flow took 5 days, calf vascular resistance 3 days and calf venous capacitance 7 days to return to within normal levels.(ABSTRACT TRUNCATED AT 400 WORDS)     

Hemodynamic comparison of primary venous or arteriolar dilatation and the subsequent effect of furosemide in left ventricular failure after acute myocardial infarction

The hemodynamic effect of venous dilatation (intravenous isosorbide dinitrate [ISDN]) and arteriolar dilatation (intravenous hydralazine), both as firstline treatment and then combined with intravenous furosemide, were evaluated in a randomized, between-group comparison in 20 men with severe acute left-sided cardiac failure after myocardial infarction (MI). Both ISDN (50 to 200 micrograms/kg/hour) (Group 1) and hydralazine (0.15 mg/kg) (Group 2) reduced systemic arterial pressure (p less than 0.05) and vascular resistance (p less than 0.05). Pulmonary artery occluded pressure was reduced (p less than 0.01) only by ISDN, whereas heart rate (p less than 0.01), cardiac output (p less than 0.01) and stroke volume (p less than 0.05) were increased only after hydralazine. After ISDN, furosemide (1 mg/kg) decreased left-sided cardiac filling pressure by 1 mm Hg (p greater than 0.05), whereas after hydralazine, furosemide in a similar dose reduced pulmonary artery occluded pressure by 5 mm Hg (p less than 0.01). In both groups of patients, furosemide transiently increased systemic arterial pressure (p less than 0.05). Cardiac output was reduced (p less than 0.05) and systemic vascular resistance increased (p less than 0.05) in Group 1 patients after furosemide. Similar changes in both variables in Group 2 patients did not attain statistical significance. In conclusion, ISDN-induced venous dilatation is preferable to primary arteriolar dilatation by hydralazine as first-line treatment in acute left-sided cardiac failure. However, hydralazine and furosemide in combination were equally effective in reducing pulmonary artery occluded pressure and increasing cardiac output. The influences of each regimen on prognosis await further investigation.     

Peripheral circulatory effects of insulin in diabetes

Peripheral circulatory effects of insulin were studied in the diabetic patients with and without autonomic neuropathy. Forearm blood flow, calf venous volume and calf venous distensibility were measured by strain gauge plethysmography. In the diabetic patients with autonomic neuropathy, mean blood pressure fell from 96 +/- 5 to 88 +/- 5 mmHg after an intravenous injection of 4 U of monocomponent insulin (p less than 0.001). Forearm vascular resistance decreased from 53.99 +/- 8.29 to 45.88 +/- 7.76 mmHg X ml-1 X 100ml-1 X min-1 after insulin (p less than 0.01). Insulin increased calf venous volume from 1.20 +/- 0.19 to 2.23 +/- 0.44 ml/100ml (p less than 0.05) and calf venous distensibility from 0.039 +/- 0.004 to 0.082 +/- 0.016 ml/mmHg (p less than 0.05). In contrast, in the diabetic patients without autonomic neuropathy, there were no significant changes in the mean blood pressure, forearm vascular resistance, calf venous volume and calf venous distensibility. Symptoms of hypoglycaemia did not occur in any patient. These results suggest that insulin has a vasodilator action on both resistance and capacitance vessels, which may be one of the main factors in insulin-induced hypotension.     

Alpha-receptor restriction of coronary blood flow during atrial fibrillation

The effects of atrial fibrillation (AF) on coronary circulation before and after alpha-receptor blockade were studied in 14 anesthetized, open-chest dogs. AF was induced by electrical stimulation of the left atrial appendage; identical rhythmic heart rates were adjusted by left atrial pacing. During atrial pacing, coronary vascular resistance (CVR) was 0.97 +/- 0.10 mm Hg X min X 100 g/ml (resistance units [RU]), coronary blood flow (CBF) 125 +/- 14 ml/min X 100 g, and oxygen saturation 30 +/- 2%; plasma epinephrine was 193 +/- 42 pg/ml and norepinephrine 584 +/- 111 pg/ml. During AF, CVR was higher (1.16 +/- 0.11 RU, p less than 0.0005), whereas CBF (92 +/- 9 ml/min X 100 g, p less than 0.001) and coronary sinus oxygen saturation (24 +/- 2%, p less than 0.0025) were lower than during atrial pacing. When AF was induced, epinephrine increased to 333 +/- 98 pg/ml (p less than 0.05) and norepinephrine to 1,005 +/- 214 pg/ml (p less than 0.005). The large increase in plasma catecholamines suggested an activation of the sympathoadrenal system during AF. In addition, the alpha-receptor blocker phenoxybenzamine (10 mg/kg, intravenously) abolished the differences in CVR, CBF and oxygen saturation between AF and atrial pacing. The data suggest that the decrease in CBF and increase in CVR during experimentally induced AF are caused by coronary vasoconstriction, mediated by sympathetic activation of alpha receptors in the coronary vascular bed.     

Effects of alpha human atrial natriuretic polypeptide on the systemic hemodynamics and coronary circulation in patients with ischemic heart disease

Alpha human atrial natriuretic polypeptide (alpha-hANP) was intravenously infused into 7 patients with ischemic heart disease who had almost normal cardiac function at a rate of 0.025 micrograms/kg/min for 15 min. During infusion of alpha-hANP, left ventricular (LV) systolic pressure decreased from 144 +/- 19 (SD) to 129 +/- 22 mmHg (p less than 0.01), LV end diastolic pressure (EDP) from 15 +/- 5 to 13 +/- 4 mmHg (p less than 0.05), mean aortic pressure from 102 +/- 14 to 91 +/- 14 mmHg (p less than 0.01), time constant of LV pressure fall (T) from 100 +/- 15 to 88 +/- 13 msec (p less than 0.05), systemic vascular resistance (SVR) from 1711 +/- 206 to 1424 +/- 340 dynes.sec.cm-5 (p less than 0.05) and coronary vascular resistance (CVR) from 8.5 +/- 1.2 to 7.4 +/- 1.3 x 10(4) dynes.sec.cm-5 (p less than 0.05). There was a linear correlation between percent changes in SVR and those of CVR (r = 0.92, p less than 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 less than 0.05), LV dp/dt from 1558 +/- 266 to 1627 +/- 238 mmHg/sec (p less than 0.05), LV dp/dt/p from 22.9 +/- 3.2 to 25.6 +/- 3.7/sec (p less than 0.01), and myocardial oxygen consumption (from 7.9 +/- 2.4 to 9.8 +/- 2.1 ml/min, p less than 0.05), while mean right atrial and mean pulmonary arterial pressures and pulmonary vascular resistance were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of experimentally induced atrial fibrillation on coronary circulation in dogs

The influence of atrial fibrillation on coronary circulation was studied in 21 anesthetized open-chest dogs. Atrial fibrillation was induced either by local application of acetylcholine (10% in normal saline) on the left atrial appendage or by electric stimulation (2-7 volts, 2 ms, 50 Hz). When atrial fibrillation was induced (n = 10), mean aortic pressure fell and heart rate rose significantly; coronary blood flow (CBF) remained unchanged (78 +/- 6 vs. 75 +/- 5 ml/min X 100 g) while coronary vascular resistance (CVR) (1.16 +/- 0.05 vs. 0.87 +/- 0.07 [m Hg X min X 100 gl/ml [RU], p less than 0.0001) and sinus oxygen saturation (26 +/- 2 vs. 22 +/- 1%, p less than 0.05) decreased. Following the application of carbochromen (5 mg/kg in 3 min i.v.) resulting in maximal coronary dilatation, atrial fibrillation resulted in a reduction in CBF (311 +/- 48 vs. 205 +/- 30 ml/min X 100 g, p less than 0.01) and coronary sinus oxygen saturation (65 +/- 6 vs. 42 +/- 6%, p less than 0.01), while CVR (0.27 +/- 0.03 vs. 0.37 +/- 0.04 RU, p less than 0.0001) was 38 +/- 8% (p less than 0.0005) higher during atrial fibrillation than at sinus rhythm. When hearts were paced to a rate which was identical to the average heart rate at atrial fibrillation (n = 11), CBF (92 vs. 125 +/- 14 ml/min X 100 g, p less than 0.001) and sinus oxygen saturation (24 +/- 2 vs. 30 +/- 2%, p less than 0.0025) were higher and CVR (1.16 +/- 0.11 vs. 0.97 +/- 0.10 RU, p less than 0.0005) lower than during atrial fibrillation; during maximal coronary dilatation by carbochromen, pacing also resulted in a higher CBF (233 +/- 24 vs. 168 +/- 16 ml/min X 100 g, p less than 0.0005) and sinus oxygen saturation (70 +/- 3 vs. 57 +/- 2%, p less than 0.0005), while CVR (0.25 +/- 0.02 vs. 0.46 +/- 0.02 RU, p less than 0.0005) was lower than during atrial fibrillation. Thus atrial fibrillation results in a decrease in coronary vascular resistance but an increase in coronary oxygen extraction. When heart rate is controlled, the vasoconstrictor effect of atrial fibrillation becomes unmasked. Coronary vasoconstriction during atrial fibrillation appears to be greater during maximal coronary dilatation than during control.     

Hemodynamic effects of intravenous isosorbide dinitrate and nitroglycerine in acute myocardial infarction and elevated pulmonary artery wedge pressure

We compared in a randomized fashion the hemodynamic effects of intravenous (IV) isosorbide dinitrate (ISDN) and nitroglycerine (NTG) in 45 patients with acute myocardial infarction and elevated pulmonary artery wedge pressure (Paw). Titration of ISDN dose to lower Paw greater than or equal to 25 percent resulted in a fall of this parameter from 32 +/- 8 to 24 +/- 5 mm Hg and was associated with a fall in mean blood pressure (96 +/- 15 to 90 +/- 14 mm Hg, p less than 0.05), systemic vascular resistance (1715 +/- 572 to 1548 +/- 414 dynes X s X cm-5, (p less than 0.05), pulmonary vascular resistance (182 +/- 106 to 154 +/- 78 dynes X s X cm-5, p less than 0.05) and mean right atrial pressure (11 +/- 4 to 7 +/- 4 mm Hg, p less than 0.05). In addition, ISDN significantly (p less than 0.05) increased cardiac index from 2.37 +/- 0.54 to 2.54 +/- 0.59 L/min/m2, stroke volume index from 28 +/- 8 to 31 +/- 8 ml/m2, and stroke work index from 28 +/- 11 to 31 +/- 12 g X m/m2. The ISDN dose ranged from 50 to 533 micrograms/min (mean +/- SD 326 +/- 176 micrograms/min) and could not be predicted from baseline hemodynamic values. A comparison between the effect of ISDN and NTG in doses producing comparable reduction in Paw showed similar hemodynamic changes. It was concluded that IV ISDN in patients with elevated mean pulmonary artery wedge pressure due to acute myocardial infarction results in a decrease in right and left ventricular preload and afterload and improvement of cardiac output and cardiac work. The effective dose ranges from 50 to 533 micrograms/min and cannot be predicted from baseline hemodynamic values. In doses producing comparable reduction in Paw, ISDN and NTG had similar hemodynamic effects.     

ACE inhibition attenuates sympathetic coronary vasoconstriction in patients with coronary artery disease.

BACKGROUND. In humans, angiotensin converting enzyme (ACE) inhibition attenuates the vasoconstriction induced by sympathetic stimulation in a number of peripheral districts. Whether this is also the case in the coronary circulation is unknown, however. METHODS AND RESULTS. In nine normotensive patients with angiographically assessed coronary atherosclerosis, we measured the changes in mean arterial pressure (intra-arterial catheter), heart rate, rate-pressure product (RPP), coronary sinus blood flow (CBF, thermodilution method), and coronary vascular resistance (CVR, ratio between mean arterial pressure and CBF) induced by the cold pressor test (CPT, 2 minutes) and diving (30 seconds), i.e., two stimuli eliciting a sympathetic coronary vasoconstriction. The measurements were performed in the control condition and 30 minutes after captopril 25 mg p.o. In the control condition, CPT caused an increase in mean arterial pressure and heart rate. Despite the increase in RPP (+20.7 +/- 3.2%, p less than 0.01), CBF did not change and CVR increased (+12.2 +/- 4.0%, p less than 0.05). diving caused an increase in mean arterial pressure and a reduction in heart rate. RPP increased (+14.3 +/- 3.5%, p less than 0.01), but despite this increase, there was a reduction in CBF and a marked increase in CVR (+37.3 +/- 7.4%, p less than 0.01). Captopril did not modify the blood pressure and heart rate responses to both stimuli except for a slight accentuation of the bradycardia to diving. Despite the unchanged or only slightly reduced RPP response, the increase in CVR was markedly and significantly attenuated (p less than 0.01). CONCLUSIONS. ACE inhibition attenuates sympathetic coronary vasoconstriction in patients with coronary artery disease. This is probably due to removal of the facilitating influence of angiotensin II on sympathetic modulation of coronary vasomotor tone.     

Acute respiratory acidosis decreases left ventricular contractility but increases cardiac output in dogs

To understand the cardiovascular response to respiratory acidosis, we measured hemodynamics, left ventricular pressure, and left ventricular volume (three ultrasonic crystal pairs) during eucapnia and respiratory acidosis in 10 fentanyl-anesthetized open-chest dogs. Left ventricular contractility was assessed primarily by measuring the slope (Emax) and intercept (V0) of the left ventricular end-systolic pressure-volume relation determined by combining end-systolic points from a vena caval occlusion and from brief aortic cross-clamping. Respiratory acidosis (pH 7.09, Pco2 92 mm Hg) reduced contractility by a decrease in Emax (11.4 to 9.2 mm Hg/ml, p less than 0.01) with no change in V0. Despite this, cardiac output increased (1.7 to 2.1 l/min, p less than 0.01), and heart rate increased (96 to 121 beats/min, p less than 0.05), with no change in blood pressure. Systemic vascular resistance fell by 26% (p less than 0.01). During eucapnia, propranolol reduced Emax (11.4 to 4.6 mm Hg/ml, p less than 0.01) with no change in V0. After propranolol treatment, respiratory acidosis further reduced Emax (4.6 to 3.6 mm Hg/ml, p less than 0.05) and increased end-systolic volume more than before propranolol (p less than 0.001). Now cardiac output did not increase even though heart rate increased (81 to 106 beats/min, p less than 0.001) and systemic vascular resistance fell by 20% (p less than 0.01). We conclude that the effect of respiratory acidosis on the circulation is to increase venous return (equals cardiac output) in the face of decreased left ventricular contractility. The beta-adrenergic response to respiratory acidosis substantially ameliorated the increase in end-systolic volume and supported the increase in venous return but did not alter the associated tachycardia or vasodilation. Respiratory acidosis, like propranolol treatment, decreases contractility by decreasing Emax.     

Effects of long-term lercanidipine or hydrochlorothiazide administration on hypertension-related vascular structural changes

OBJECTIVES: Vascular remodelling and hypertrophy represent early therapeutic targets of antihypertensive treatment. The present study was aimed at assessing the effects of 1-year administration of the highly vasoselective calcium-channel blocker lercanidipine (10 mg/day) or the diuretic compound hydrochlorothiazide (25 mg/day) on hypertension-related vascular alterations. The study was also aimed at assessing whether and to what extent: (i) pharmacological regression of vascular hypertrophy is related only to the blood pressure (BP) reduction "per se" or also to the specific ancillary properties of a given drug and (ii) treatment provides restoration of vascular function indicative of normal vascular structure. DESIGN AND METHODS: In 26 untreated patients with mild-to-moderate essential hypertension sphygmomanometric and finger BP, heart rate, forearm and calf blood flow (venous occlusion plethysmography) and corresponding vascular resistance (forearm and calf vascular resistance: FVR and CVR) were assessed before and following 6 and 12 months of either lercanidipine or hydrochlorothiazide administration. Vascular resistance was also evaluated following a local ischaemic stimulus (FVR(min) and CVR(min)) in order to assess the effects of treatment on arteriolar structural alterations. RESULTS: For superimposable BP reductions, lercanidipine caused FVR and CVR to decrease significantly more than hydrochlorothiazide. Similarly, the FVR(min) and CVR(min) reductions induced by lercanidipine were markedly and significantly greater than those caused by hydrochlorothiazide (-46.1% and -40.9% vs -22.5% and -19.9%, p < 0.01 for both). FVR(min), and CVR(min), however, remained higher than those found in 10 age-matched normotensive individuals. CONCLUSIONS: These data provide evidence that, compared to hydrochlorothiazide, lercanidipine favours a greater regression of the vascular structural changes associated with hypertension, probably through its "ancillary" properties. Lercanidipine, however, does not allow restoration of a "normal" vascular structure, thereby suggesting that vascular hypertrophy is only in part a reversible phenomenon.     

Effects of indomethacin on pulmonary hemodynamics and gas exchange in patients with pulmonary artery hypertension, interference with hydralazine

To assess the ability of indomethacin (Indo) to influence pulmonary vascular tone in patients with chronic lung disease, we studied the hemodynamic and gas exchange alterations induced by a 50-mg indomethacin infusion in 10 patients suffering from varying degrees of pulmonary artery hypertension and hypoxemia. The most pronounced effects were observed 3 h after Indo administration. Mean systemic arterial pressure (Psa) increased from 76 +/- 4 to 86 +/- 4 mm Hg (p less than 0.01), whereas mean pulmonary arterial pressure (Ppa) was unchanged. The cardiac index (CI) decreased from 3.1 +/- 0.2 to 2.8 +/- 0.2 L/min/m2 (p less than 0.02) because of the reduced heart rate, which decreased from 86 +/- 5 to 80 +/- 4 beats/min (p less than 0.05). Systemic and pulmonary vascular resistance indexes increased, respectively, from 22 +/- 2 to 27.5 +/- 2 U/m2 (p less than 0.001) and from 11.9 +/- 2 to 13.4 +/- 2 U/m2 (p less than 0.05). We measured an increase in PaO2, from 49.5 +/- 4 to 57.5 +/- 4 mm Hg (p less than 0.001) simultaneously with a reduced venous admixture, from 39.5 +/- 4 to 30.5 +/- 3% (p less than 0.001). The calculated PO2 uptake was unchanged, but mixed venous O2 tension increased from 30.5 to 33.5 mm Hg (p less than 0.01). Because Indo may interfere with the hypotensive effect of hydralazine and because hydralazine has been proposed in the treatment of patients with pulmonary hypertension, 7 of these patients also received 0.35 mg/kg hydralazine and Indo plus hydralazine (Indo + H) injected simultaneously.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relation between sympathetic outflow and vascular resistance in the calf during perturbations in central venous pressure. Evidence for cardiopulmonary afferent regulation of calf vascular resistance in humans

Vascular studies in humans have advanced the concept that, during orthostatic stress, cardiopulmonary afferents reflexly regulate vascular resistance in the forearm but exert surprisingly little if any effects on vascular resistance in the calf. In contrast, neurophysiological studies have indicated that unloading of cardiopulmonary afferents during lower body negative pressure evokes comparable increases in sympathetic outflow to the muscles of both the forearm and the calf. The aim of this study, therefore, was to determine if alterations in central venous pressure over the physiological range trigger reflex changes in muscle sympathetic outflow that not only are statistically significant but also are large enough to alter vascular resistance in the calf. To accomplish this aim, we measured calf blood flow with plethysmography and simultaneously performed microelectrode recordings of sympathetic outflow to calf muscles in conscious humans during maneuvers designed to alter the loading conditions of the cardiopulmonary afferents. We found that calf vascular resistance increased by 33 +/- 7% (mean +/- SEM, p less than 0.05) during decreases in central venous pressure produced by nonhypotensive lower body negative pressure (LBNP) and decreased by 26 +/- 5% (p less than 0.05) during increases in central venous pressure produced by nonhypertensive infusion of normal saline. These changes in calf resistance were at least as large as the changes in forearm resistance evoked by these maneuvers and were accompanied by parallel changes in peroneal muscle sympathetic nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Isosorbide dinitrate and glyceryl trinitrate: demonstration of cross tolerance in the capacitance vessels

Cross tolerance to the arterial effects of sublingual glyceryl trinitrate (GTN) has been demonstrated in subjects taking oral isosorbide dinitrate (ISDN). To determine if cross tolerance also develops in the venous system, the effects of 0.6 mg of GTN on venous capacitance were assessed before (stage A) and during (stage B) therapy with ISDN. Venous capacitance was assessed using the radionuclide blood pool method, with relative changes in regional blood volume measured in the forearm in 6 patients and the splanchnic circulation in 4 patients. Heart rate, blood pressure and blood volume were measured before and at 1-minute intervals for 10 minutes after GTN; there was less than 2% variability in regional blood volume during 6 control measurements. During stage A, 5 minutes after GTN, systolic blood pressure (mean +/- standard deviation) decreased by 14% (from 125 +/- 15 to 107 +/- 19 mm Hg, p less than 0.01) and heart rate increased by 17% (from 68 +/- 14 to 80 +/- 17 beats/min, p less than 0.001), while regional blood volume increased to 101 +/- 2% at 1 minute (difference not significant [NS]), 111 +/- 2% at 5 minutes (p less than 0.001) and 107 +/- 3% at 10 minutes (p less than 0.01) relative to baseline measurements.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of intracoronary administration of contrast media on coronary hemodynamics in a canine post ischemic reperfusion model

Hemodynamic changes due to intracoronary injections of nonionic contrast medium Omnipaque-350 (OM), ionic dimer Hexabrix (HB), and ionic contrast medium Renografin-76 (R76) were compared at baseline and during reperfusion after a 30-minute left anterior descending coronary artery (LAD) occlusion. In 11 open chest, anesthetized, and atrially paced dogs, 4 ml of either OM, HB, R76, or 0.9% NaCl were injected into the carotid-LAD bypass system. Coronary blood flow (CBF) and coronary vascular resistance (CVR) were measured before, during and after the intracoronary injection. The maximal hyperemic change (in percentage) from the preinjection value of CBF and CVR were calculated. The results at baseline and during reperfusion for CBF were: 104 +/- 14% vs. 85 +/- 10% for OM (NS); 76 +/- 11% vs. 39 +/- 9% for R76 (p less than 0.05); 57 +/- 8% vs. 33 +/- 5% for HB (P less than 0.05); and 30 +/- 7% vs. 9 +/- 4% for 0.9% NaCl (p less than 0.05). Consequently, the hyperemic changes of CVR at baseline and during reperfusion were: -49 +/- 3 vs. -42 +/- 4% for OM (NS); -44 +/- 3% vs. -24 +/- 6% for R76 (p less than 0.01); -36 +/- 3% vs. -24 +/- 4% for HB (p less than 0.05); and -18 +/- 4% vs. -7 +/- 3% for 0.9% NaCl (p less than 0.05). Thus, ischemia and reperfusion significantly dampened the coronary hemodynamic and vascular response to R76, HB, and 0.9% NaCl but not to OM. The preserved coronary vascular reserve with high flow in this canine post-ischemic reperfusion model may explain the advantage of nonionic over ionic contrast media used in emergency coronary angiography following thrombolysis.     

Dose-related cardiovascular effects of spironolactone

The aim of this study was to assess the shortterm hemodynamic effects of increasing doses of spironolactone (25, 50, and 75 mg/day) on oligurie patients (5 men, mean age 47 ± 12 years) undergoing hemodialysis for chronic renal impairment. Parameters of interest included heart rate (HR), cardiac output, systemic vascular resistance (SVR), arterial pressure, right atrial pressure, and pulmonary capillary wedge pressure (PCWP). The study also evaluated how spironolactone modified the effects on arterial and right atrial pressures and PCWP of infusion of increasing doses of norepinephrine (20, 40, and 100 ng/ kg/min) and angiotensin II (2, 4, and 10 ng/kg/ min). Compared with placebo, the lowest dose of spironolactone (25 mg/day) produced statistically significant (p < 0.05) modifications in systemic arterial pressures without a compensatory increase in cardiac output. The modifications were more pronounced at 50 and 75 mg/day, and the latter had a significant dose-dependent effect. Moreover, doses of 50 and 75 mg/day produced significant (p < 0.05) decreases in right atrial pressure and PCWP. Spironolactone administration caused the curve expressing the relation between an infused norepinephrine or angiotensin II dose and the blood pressure response to shift significantly (p < 0.05 to <0.01) to the right, and the pressor doses of norepinephrine or angiotensin II showed a significant (p < 0.05 to <0.01) dose-related increase, suggesting that treatment with spironolactone inhibited cardiovascular reactivity. This effect was observed on both the capacitance (i.e., low-pressure) and resistance (i.e., high pressure) vessels. Thus, an important dose-related effect of spironolactone on both the high- and low-pressure systems appears to play a major role in the drug's vascular and antihypertensive effects.     

Hemodynamic trial of sequential treatment with diuretic, vasodilator, and positive inotropic drugs in left ventricular failure following acute myocardial infarction

The circulatory effects induced by two sequential intravenous treatment programs with a diuretic, arteriolar or venodilator , and a positive inotropic drug were studied in a randomized between-group trial in 20 male patients with radiographic and hemodynamic evidence of left ventricular (LV) failure following acute myocardial infarction (AMI). Furosemide induced a substantial diuresis in both groups of patients, in association with reductions in LV filling pressure (p less than 0.01) and cardiac output (p less than 0.05), without significant change in heart rate or systemic arterial pressure. The addition of isosorbide dinitrate was followed by reductions in the systemic arterial (p less than 0.01) and LV filling pressures (p less than 0.01) without significant change in the heart rate or cardiac output. Hydralazine after furosemide reduced systemic vascular resistance (p less than 0.01), but the fall in mean blood pressure (p less than 0.01) was limited by the increase in cardiac output (p less than 0.01); heart rate was also increased (p less than 0.01) and LV filling pressure fell (p less than 0.05). The final addition of the beta-1 adrenoceptor agonist, prenalterol, increased systemic arterial systolic pressure (p less than 0.05), cardiac output (p less than 0.05), and heart rate (p less than 0.01), and reduced systemic vascular resistance (p less than 0.01) in both groups; these changes were greatest in those pretreated with furosemide and isosorbide dinitrate. In both treatment pathways compared with control the reductions in systemic vascular resistance and left heart filling pressure were accompanied by increases in heart rate and cardiac output without substantial changes in systemic blood pressure. Which of these hemodynamic pathways offers the optimum prognosis awaits further study.     

Regional distribution of cardiac output at rest and during exercise in patients with exertional angina pectoris before and after nifedipine therapy

The short-term effects of sublingual nifedipine (20 mg) on cardiac output and its distribution at rest and during exercise were evaluated by measurement of iliofemoral blood flow and cardiac output in 10 men with stable angina pectoris controlled by metoprolol. At rest, nifedipine significantly decreased iliofemoral vascular resistance from 294 +/- 36 to 165 +/- 29 dynes.s.cm-5.10(2) (p less than 0.01) and significantly increased iliofemoral blood flow from 0.34 +/- 0.04 to 0.57 +/- 0.11 liters/min (p less than 0.05). Systemic vascular resistance was reduced from 19 +/- 1 to 13 +/- 1 dynes.s.cm-5.10(2) (p less than 0.001) and cardiac output increased significantly from 4.7 +/- 0.3 to 5.8 +/- 0.5 liters/min (p less than 0.05). Mean arterial pressure decreased significantly and heart rate increased significantly. During maximal upright bicycle exercise during nifedipine therapy, iliofemoral vascular resistance and leg blood flow were unchanged compared with control (23 +/- 2 versus 21 +/- 3 dynes.s.cm-5.10(2) and 4.7 +/- 0.5 versus 4.4 +/- 0.6 liters/min), cardiac output remained significantly increased (12.8 +/- 0.8 to 15.2 +/- 1.2 liters/min, p less than 0.05) and systemic vascular resistance remained significantly reduced (8 +/- 1 to 5 +/- 1 dynes.s.cm-5.10(2); p less than 0.001). The proportion of cardiac output distributed to the working lower limbs was significantly reduced at all exercise levels. In summary, nifedipine caused a redistribution of cardiac output by vasodilating nonexercising vascular beds without altering the locally mediated vasodilation in exercising muscle. In patients with coronary artery disease given nifedipine therapy, an increase in exercise tolerance is due to relief of myocardial ischemia rather than to increased peripheral oxygen delivery.     

L-arginine ameliorates the abnormal sympathetic response of the dysfunctional human coronary microvasculature

A nitric oxide (NO)-related defect may contribute to abnormal coronary sympathetic responses that can cause ischemia in patients with endothelial dysfunction. Because L-arginine, the NO synthase (NOS) precursor, augments NO bioactivity, we hypothesized that L-arginine would improve dysfunctional coronary sympathetic responses. Eleven patients with atherosclerosis or its risk factors were challenged with the cold pressor test, a specific provocative test of cardiac sympathetic activity, after 3 separate and sequential intracoronary infusions, as follows: 1) Normal saline; 2) L-NMMA, a competitive inhibitor of NOS; and 3) L-arginine. Study patients exhibited abnormal microvascular responses with coronary vascular resistance (CVR) increasing by 22.3 +/- 9.7% (mean +/- 1 SEM), p < 0.01. In addition, the change in coronary blood flow (CBF) did not correlate with the change in rate pressure product (RPP), r = -0.29, p = NS, suggesting an uncoupling of CBF from cardiac work. In the presence of L-NMMA, the CVR response, 10.3 +/- 9.8%, did not differ from the baseline response, and there was no relationship between the changes in CBF and RPP, r = 0.13, p = NS. In contrast, L-arginine ameliorated the CVR response, -3.2 +/- 3.1%, p < 0.05 vs baseline response, and restored the normal correlation between the changes in CBF and RPP, r = 0.74, p < 0.01. L-arginine not only improved abnormal microvascular responses to sympathetic activation, but it also restored the coupling that normally exists between coronary blood flow and cardiac work. L-arginine warrants further investigation as a therapy for coronary artery disease.     

Hemodynamic management in clinical acute hypoxemic respiratory failure. Dopamine vs dobutamine

We investigated short-term hemodynamic effects of dopamine and dobutamine in eight patients with acute hypoxemic respiratory failure. We tested the hypothesis that for a similar increase in cardiac output, left ventricular filling pressure (pulmonary capillary wedge pressure [PCWP]) would increase with dopamine and decrease with dobutamine. Dopamine increased cardiac output (p less than 0.05), stroke volume (p less than 0.05), and PCWP (p less than 0.01). Cardiac output increased almost 20 percent when PCWP increased 50 percent with dopamine. In contrast, despite a mean 30 percent increase in cardiac output with dobutamine (p less than 0.01), PCWP decreased. In six of these patients, left ventricular end-diastolic volumes and end-systolic volumes were measured using scintigraphic techniques. In all patients, end-diastolic volume increased with dopamine (p less than 0.05); and in four of six, end-systolic volume increased. In contrast, with dobutamine, in five of six patients, end-diastolic volume decreased; and in all six patients, end-systolic volume decreased. There was a small increase in intrapulmonary shunt with both drugs. We conclude that if an inotropic agent is required to increase cardiac output in patients with acute hypoxemic respiratory failure, dobutamine is probably preferred over dopamine.     

Disparate effects of substance P on systemic and coronary beds in conscious dogs.

BACKGROUND. Previous studies in anesthetized animals indicated that substance P is a coronary and peripheral vasodilator. However, coronary vasodilation was only transient perhaps because of tachyphylaxis. In the present study, the steady-state effects of intravenous substance P on systemic and coronary beds were investigated in conscious, instrumented dogs. METHODS AND RESULTS. With intact autonomic reflexes, 5 ng/kg/min i.v. substance P resulted in increases (p less than 0.01) in cardiac output by 22 +/- 5%, in decreases (p less than 0.01) in mean arterial pressure by 9 +/- 2%, and in total peripheral resistance by 23 +/- 4% 7-9 minutes after the beginning of substance P infusion. Heart rate increased (p less than 0.01) by 35 +/- 7% and left ventricular dP/dt (p less than 0.05) by 13 +/- 4%. In this situation, coronary blood flow decreased (p less than 0.01) by 19 +/- 4% and coronary vascular resistance increased (p less than 0.05) by 13 +/- 5%. Myocardial oxygen delivery was reduced (p less than 0.05) by 13 +/- 5% and the arteriovenous oxygen difference widened (p less than 0.01). After ganglionic blockade, increases in cardiac output, heart rate, and left ventricular dP/dt with substance P administration were abolished, but total peripheral resistance and mean arterial pressure decreased (p less than 0.01) by 12 +/- 3% respectively. Under these conditions, coronary blood flow decreased (p less than 0.01) by 37 +/- 5% and coronary vascular resistance increased (p less than 0.01) by 47 +/- 8%, which were more (p less than 0.01) than control responses. In this situation, myocardial oxygen delivery was reduced (p less than 0.01) by 37 +/- 4% and the arteriovenous oxygen difference widened (p less than 0.01). Intracoronary infusion of substance P (0.4 ng/kg/min) resulted in significant and sustained decreases in coronary blood flow, which were similar before and after ganglionic blockade. CONCLUSIONS. Thus, in conscious dogs, systemic vasodilation is the prevailing effect of substance P, but paradoxically, this peptide simultaneously elicits coronary vasoconstriction.