Significant Decrease In Cardiac Index Research Articles

Effects of reserpine administration in two models of portal hypertension in rats

The effects of reserpine were investigated in two models of portal hypertension in rats. Twenty-four hours after 1 mg/kg of reserpine was administered intraperitoneally to normal and portal vein stenosed rats, the cardiac index, mean arterial pressure, heart rate, and portal pressure were significantly decreased compared with normal and portal vein stenosed rats receiving placebo. In addition, the portal tributary blood flow was significantly decreased in portal vein stenosed rats receiving reserpine, but was unchanged in normal rats. In cirrhotic rats receiving a single dose of reserpine, 0.1 mg/kg intraperitoneally for 24 h, there were significant decreases in cardiac index, mean arterial pressure and heart rate compared with cirrhotic rats receiving placebo, while the portal pressure and portal tributary blood flow followed a decreasing trend after reserpine administration. The degree of hemodynamic change was similar in the groups of rats receiving reserpine, even though cirrhotic rats received lower doses than either normal or portal vein stenosed rats. This study suggests enhanced sympathetic nervous activity observed in cirrhotic rats.

CHANGES IN CARDIAC INDEX AND ESTIMATED SYSTEMIC VASCULAR RESISTANCE DURING INDUCTION OF ANAESTHESIA WITH THIOPENTONE, METHOHEXITONE, PROPOFOL AND ETOMIDATE

Changes in cardiac index (CI) and estimated systemic vascular resistance (ESVR) were assessed non-invasively using pulsed Doppler ultrasound during induction of anaesthesia. Ninety-six ASA I patients were allocated randomly to one of four groups to receive alfentanil 8 micrograms kg-1 followed by a dose of thiopentone, methohexitone, propofol or etomidate sufficient to obtund the eyelash reflex. CI increased significantly by 8% 1 min after administration of both methohexitone (P < 0.05) and propofol (P < 0.05), returning to pre-induction values thereafter. CI increased after thiopentone but the increase was not statistically significant. There was a significant decrease in CI of 16% after induction with etomidate (P < 0.001). ESVR decreased significantly from pre-induction values by 18% after methohexitone (P < 0.001) and 23% after propofol (P < 0.001). ESVR in the thiopentone group decreased, but this was not statistically significant. ESVR increased significantly by 12% 1 min after induction of anaesthesia with etomidate (P < 0.05) and then decreased towards pre-induction values. The results suggest that the cardiostability of etomidate may not be as complete in all groups of patients as previous studies have suggested.

Hemodynamic effects of anesthesia in patients chronically treated with angiotensin-converting enzyme inhibitors.

Angiotensin-converting enzyme inhibitors (ACEIs) are increasingly used in the treatment of cardiovascular disease, but recent reports have warned of some hemodynamic risk (hypotension and bradycardia) when associated with anesthesia. To assess the hemodynamic effects of induction of anesthesia in patients chronically treated with ACEIs, 16 hypertensive patients scheduled for coronary artery bypass graft surgery (n = 12) or vascular surgery (n = 4) were studied. Eight of them were chronically treated (for at least 1 mo) with ACEIs (ACEI group), and the remaining eight (control group) were treated with other classes of antihypertensive drugs. Induction of anesthesia, which consisted of flunitrazepam (0.03 mg/kg), fentanyl (0.006 mg/kg), and pancuronium (0.1 mg/kg) IV, was followed by a significant decrease in mean arterial blood pressure from baseline in both groups (by 16.8% in controls [P = 0.001] and 33.5% in ACEI-treated patients [P = 0.001] [P = 0.041 between groups]). In control patients, mean arterial blood pressure decrease was only associated with a significant decrease in cardiac index (-18%, P = 0.014). In ACEI-treated patients, the arterial blood pressure decreases were associated with consistent reductions in pulmonary capillary wedge pressure (-26.4%; P = 0.035) and cardiac index (-23.9%; P = 0.001). Systemic vascular resistance index and heart rate were moderately changed (-14.2% and -4.5%, respectively). Rapid restoration of arterial blood pressure was obtained in all ACEI-treated patients, mainly with the intravenous administration of 0.4 to 0.7 L of lactated Ringer's solution. Phenylephrine (0.38 +/- 0.9 mg) was, however, required in four patients when mean arterial blood pressure was less than 60 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic evaluation of bisoprolol after coronary artery surgery in patients with altered left ventricular function

Bisoprolol is a new cardioselective beta1 adrenergic blocking agent without intrinsic sympathomimetic activity but with minimal effects on myocardial contractility. Bisoprolol was compared to propranolol in 24 patients after cardiac surgery for coronary artery bypass graft (CABG). Each patient had been treated preoperatively with beta-blocking agents and had a cineangiographic left ventricular ejection fraction between 35% and 55%. Patients were randomized to receive orally either 10 mg of propranolol three times a day or 5 mg of bisoprolol once a day. Both drugs resulted in a significant and similar decrease in heart rate. This was associated with significant decreases in cardiac index, stroke index, and thermodilution right ventricular ejection fraction 6 hours after administration of propranolol, but not after bisoprolol. Systolic function measured by Doppler techniques significantly increased in the 10 postoperative days in patients under bisoprolol but not significantly after propranolol. Each drug was well tolerated during the 10 postoperative days, and the recovery was uneventful in each patient. These results indicate that in patients with altered systolic function after CABG, bisoprolol is susceptible to reduce heart rate with less cardiovascular alteration than propranolol.

Dipyridamole-thallium myocardial scanning in the pre-operative assessment of patients undergoing abdominal aortic aneurysmectomy

Dipyridamole thallium scanning (DTS) is an imaging technique with good sensitivity for coronary artery disease (CAD). The purpose of this study was to compare the haemodynamic courses and the correlation between pulmonary capillary wedge pressure (PCWP) and central venous pressure (CVP) in patients with normal DTS (Group 1: n = 12) with those whose scans demonstrated CAD (Group 2: n = 11). Haemodynamic profiles were obtained prior to anaesthesia and at several times during surgery. The haemodynamic courses in both groups were similar with significant decreases in cardiac index, stroke index, and left ventricular stroke work index during aortic cross-clamping compared with values prior to anaesthesia. There were no significant changes in PCWP and CVP throughout the study. The correlations between PCWP and CVP were significant in both groups as were the correlations between the changes in PCWP and the changes in CVP observed at the time of cross-clamping. These correlations all had large standard errors of the estimate, however, making it impossible to predict the PCWP from the CVP with precision. It is concluded that, in a limited study population, an abnormal DTS did not identify patients in whom the PCWP and CVP correlated poorly during abdominal aortic aneurysmectomy.

Determination of right ventricular volumes during aortic surgery

The aim of the present study was to evaluate right ventricular (RV) preload by measurements of right ventricular volumes during aortic clamping and unclamping. Nine patients (aged 67 ± 9 years) undergoing infrarenal aortic aneurysmectomy were monitored with a pulmonary artery catheter equipped with a fast-response thermistor, allowing determination of RV volumes by the thermodilution technique. Anesthesia consisted of a continuous infusion of alfentanil and 50% N20. Aortic clamping resulted in a significant decrease in cardiac index (CI) and a significant increase in systemic vascular resistance (SVR). There was no significant change in right ventricular ejection fraction (RVEF) (from 35% ± 6% to 33% ± 8%) in the presence of a significant decrease in stroke index (from 37.2 ± 9.8 to 31.1 ± 10.0 mL/beat/m 2, P < 0.05), indicating a significant decrease in RV end-diastolic volume (from 106 ± 17 to 92 ± 19 mL, P < 0.01). There were no significant changes in cardiac filling pressures. Aortic unclamping was associated with a significant increase in CI and a significant decrease in SVR. There were no significant changes in cardiac filling pressures, RVEF, or RV volumes. Measurements of RV volumes indicated that aortic clamping resulted in a decrease in RV preload, which is usually not demonstrated by measurements of right atrial pressure alone.

Long-term hemodynamic effects of ketanserin, a 5-hydroxytryptamine blocker, in portal hypertensive patients.

Ketanserin, a 5-hydroxytryptamine-2 receptor blocker, has been shown to decrease portal pressure in recent acute hemodynamic studies that have been performed both in experimental animals and portal hypertensive patients. The present study was designed to investigate the effects of chronic oral administration of ketanserin in portal hypertensive patients with cirrhosis. The mean baseline hepatic venous pressure gradient in the 13 patients with alcoholic cirrhosis who completed the study was 15.7 +/- 2.7 mmHg. It decreased significantly to 13.3 +/- 2.0 mmHg (p less than 0.001) after ketanserin was administered at a mean dose of 51 mg per day for a mean period of 32 days. This 14.6% reduction in hepatic venous pressure gradient resulted mainly from a decrease in mean wedged hepatic venous pressure (from 22.2 +/- 4.0 to 20.1 +/- 3.6 mmHg) and was accompanied by significant decreases in cardiac index (18.8%) and in mean arterial pressure (8.1%). However, changes in cardiac index or in mean arterial pressure were not predictive of modifications in the hepatic venous pressure gradient. Eight of 16 patients entered in the study developed side effects, the most significant being a reversible portosystemic encephalopathy, which occurred in three patients who had poor liver function. This study confirms evidence in favor of a role for 5-hydroxytryptamine in portal hypertension and adds a new group of agents for the chronic treatment of portal hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetic and pharmacodynamic interactions between nisoldipine and propranolol

The pharmacokinetic and pharmacodynamic effects of nisoldipine, a 1,4-dihydropyridine calcium entry blocker, and the lipophilic beta-adrenoceptor blocker propranolol were assessed alone and in combination in 12 healthy men. Oral nisoldipine, 20 mg, or placebo was followed 1 hour later by propranolol, 40 mg, or placebo using a randomized, crossover, double-blind design. Nisoldipine significantly increased the AUC (+43%) and peak plasma drug concentration (Cmax) (+68%) of propranolol resulting in a higher degree of beta-adrenoceptor blockade (as assessed by isoproterenol). Conversely, nisoldipine's AUC (+30%) and Cmax (+57%) were increased with concomitant administration of propranolol. Nisoldipine did not affect blood pressure but caused significant decrease in total peripheral resistance (TPR) and increases in plasma catecholamines and cardiac index. Forearm vascular resistance and blood flow changed more markedly than did TPR and cardiac index. In contrast, propranolol had little effect on forearm hemodynamics despite significant decreases in cardiac index and increases in TPR. The data are compatible with changes in hepatic blood flow, accounting for the pharmacokinetic interaction of nisoldipine and propranolol. Different vascular beds appear to contribute to the effects of nisoldipine vs. propranolol on peripheral resistance.

Cardiovascular effects of indapamide in hypertensive patients with or without renal failure: A dose-response curve

Fifteen patients with mild-to-moderate hypertension (10 with normal and five with decreased renal function) were studied after treatment with placebo and low (1 mg), intermediate (2.5 mg), and high (5.0 mg per day) doses of indapamide, each for four weeks. Six patients—five with normal renal function—were classified as nonresponders (decrease in diastolic blood pressure less than 5 mm Hg). The remaining nine patients had dose-related decreases in blood pressure. Patients with or without renal failure showed similar decreases in blood pressure. Blood pressure reduction was associated with a significant decrease in cardiac index in the responders at the highest dose, related to a decrease in left ventricular end-diastolic dimension and stroke volume, whereas heart rate did not increase. This apparent decrease in venous return was associated with a significant decrease in body weight but not plasma volume in the responders. Indapamide did not change plasma norepinephrine levels, but decreased pressor responsiveness to exogenous norepinephrine. Responders had lower initial plasma renin activity and a smaller absolute increase in plasma renin activity while receiving indapamide, whereas angiotensin II pressor responsiveness was decreased more. The results presented indicate that the blood pressure lowering effect of indapamide in the present patient population is observed with or without renal failure and is associated with a decrease in pressor reactivity. In nonresponders, compensatory mechanisms (e.g., renin) may negate the antihypertensive effect of indapamide.

Cardiovascular effects of indapamide in hypertensive patients with or without renal failure: A dose-response curve

Fifteen patients with mild-to-moderate hypertension (10 with normal and five with decreased renal function) were studied after treatment with placebo and low (1 mg), intermediate (2.5 mg), and high (5.0 mg per day) doses of indapamide, each for four weeks. Six patients—five with normal renal function—were classified as nonresponders (decrease in diastolic blood pressure less than 5 mm Hg). The remaining nine patients had dose-related decreases in blood pressure. Patients with or without renal failure showed similar decreases in blood pressure. Blood pressure reduction was associated with a significant decrease in cardiac index in the responders at the highest dose, related to a decrease in left ventricular endodiastolic dimension and stroke volume, whereas heart rate did not increase. This apparent decrease in venous return was associated with a significant decrease in body weight but not plasma volume in the responders. Indapamide did not change plasma norepinephrine levels, but decreased pressor responsiveness to exogenous norepinephrine. Responders had lower initial plasma renin activity and a smaller absolute increase in plasma renin activity while receiving indapamide, whereas angiotensin II pressor responsiveness was decreased more. The results presented indicate that the blood pressure lowering effect of indapamide in the present patient population is observed with or without renal failure and is associated with a decrease in pressor reactivity. In nonresponders, compensatory mechanisms (e.g., renin) may negate tne antihypertensive effect of indapamide.

The hemodynamic effects of ventricular pacing with and without atrioventricular synchrony in patients with normal and diminished left ventricular function

The relative hemodynamic effects of heart rate, inotropic state, and atrioventricular (AV) synchrony during ventricular pacing were evaluated in 10 patients with normal left ventricular ejection fraction (LVEF) (0.66 ± 0.07, mean S.D.) and in eight patients with a diminished LVEF (0.34 ± 0.18). Hemodynamics were measured at AV intervals of 130, 0, and −130 msec during ventricular pacing at a baseline rate that was 10 pulses/min greater than the resting heart rate, at 130 pulses/min alone, and at 130 pulses/min during continuous intravenous infusion of dobutamine. During baseline ventricular pacing and during ventricular pacing at 130 pulses/min with and without dobutamine, both groups of patients had a significant decrease in cardiac index, stroke volume index, and stroke work index when the AV pacing interval was decreased from 130 to 0 msec. The observed decrease in these three hemodynamic variables was similar when patients with diminished LVEF were compared to patients with normal LVEF. No further significant decrease in cardiac index, stroke volume index, and stroke work index occurred in either group when the AV interval was changed from 0 to −130 msec during baseline ventricular pacing or during ventricular pacing at 130 with and without dobutamine. Beneficial hemodynamic effects occur during ventricular pacing when AV synchrony is maintained at resting heart rates and during increases in heart rate and inotropic state in patients with normal and diminished LVEF.

OPTIMAL POSITIVE END-EXPIRATORY PRESSURE (PEEP) IN INFANTS AND CHILDREN WITH ACUTE RESPIRATORY FAILURE

PEEP has become the mainstay m the treatment of hypoxemic acute respiratory failure (ARF). While PEEP improves oxygenation by decreasing intrapulmonary shunting, it may also impair cardiac output and hence decrease oxygen delivery (O2D) despite increased arterial oxygen content (CaO2). Since optimizing O2D is the goal of therapy in ARF, we sought to determine whether the level of PEEP which results in maximal O2D can be estimated using noninvasive measurements of lung compliance (C). We studied 14 normovolemic children, aged 2 wks to II yrs, with ARF due to pneumonia or ARDS. Indicator dilution cardiac index (CI), arterial O2 partial pressure (PaO2), CaO2, C, and O2D were determined at 0, 3, 6, 9, 12 and 15 cm H2O PEEP. Tidal volume and FiO2 were held constant The level of PEEP (m±SD) at which O2D was maximal was 5.8±5.3 cm, and ranged from 0-15 cm in individual pts. PEEP of maximal C averaged 8.5±6 cm (range 0-15 cm) and was the same as PEEP of maximal O2D in 6 pts (43%) but higher (7 pts) or lower (1 pt) than PEEP of maximal O2D in the remainder; no consistent relationship between O2D and C was observed. PEEP of maximal CI was identical to PEEP of maximal O2D in all pts; higher levels of PEEP were associated with a significant decrease in CI, from 5.47±2 L/min/m2 at PEEP of maximal O2D to 4.39±2 L/min/m2 at PEEP 9 cm above that of maximal O2D. PEEP of maximal PaO2 averaged 12.2±4 cm (range 0-15 cm), and corresponded to PEEP of lowest O2D in 7 pts. At levels of PEEP above that of maximal O2D, PaO2 continued to increase significantly, from 115±40 torr at PEEP of maximal O2D to 145±75 torr at PEEP 9 cm above that of maximal O2D. We conclude that PEEP of maximal C does not reliably predict PEEP of best O2D in children with ARF. Because PaO2 continues to rise at levels of PEEP which cause significant decline in CI, maximizing PaO2 will not optimize O2D unless therapy to maintain CI is also employed.

The effect of rapid resuscitation upon cardiac index following thermal trauma in a porcine model.

Minipigs were divided into four experimental groups: nonburned control (C); burn, minimal resuscitation (MR); burn, standard resuscitation (SR); and burn, rapid resuscitation (RR). Resuscitation was begun 30 minutes postburn and hemodynamics were measured through 24 hours postburn. At 30 minutes postburn, the three burn groups demonstrated a significant decrease in cardiac index % (CI%). At 1 1/2 hours postburn, the RR group CI% was significantly greater than for the SR group and not significantly different from that of controls. At 2 hours postburn, fluid was abruptly decreased in the RR group and the salutary effect on CI promptly dissipated. In this model, the early decrement in CI following thermal injury is responsive to rapid resuscitation, concluding that the etiology of decreased CI following thermal trauma is at least partially due to inadequate volumes of fluid administration in the early postburn period.

No involvement of antidiuretic hormone in acute antidiuresis during PEEP ventilation in humans.

Decreased urinary output (Vu ml/min) after institution of PEEP is attributed to a variety of mechanisms including decreased cardiac output and renal blood flow (RBF), activation of neurohormonal reflexes, increased catecholamines, plasma renin activity (PRA), and antidiuretic hormone (ADH) release. To evaluate these factors, seven normovolemic patients (36 yr +/- 13 SD), free of preexisting lung, cardiac, or renal disease, requiring continuous mandatory ventilation for neurologic reasons were studied. The authors measured or calculated: total blood volume (TBV) (51Cr); right atrial, pulmonary arterial, pulmonary wedge, and systemic pressures, cardiac index (CI); renal plasma flow (RPF) (iodohippurate sodium 131I [131I PAH] clearance); glomerular filtration rate (GFR) (creatinine clearance), free water clearance (CH2O), osmolal clearance (Cosm), fractional excretion of sodium (FENa+) and potassium (FEK+); and plasma renin activity (PRA) (ng X ml-1 X h-1), plasma ADH (pg/ml; radioimmunoassay), epinephrine (E in pg/ml), and norepinephrine (NE in pg/ml) (double-isotope radioenzymatic assay). Two conditions were studied after 90-min steady state: 1) zero PEEP (ZEEP); and 2) 15 cmH2O PEEP. PEEP caused a significant decrease in CI (-21%; P less than 0.01) and RPF (-19%; P less than 0.05) without significant decrease in GFR. A significant decrease in Vu (-55%; P less than 0.05), FENa+ (-39%; P less than 0.05) and Cosm (-36%; P less than 0.25) occurred without modification in CH2O. Plasma ADH remained in the normal range and did not increase when PEEP was applied.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of elevated coronary sinus pressure on left ventricular function after the Fontan operation: An experimental and clinical correlation

An experimental model was devised to evaluate the effects of elevated coronary sinus pressure on left ventricular performance. Thirteen mongrel dogs were used. The coronary sinus was cannulated and its entire blood flow diverted into a reservoir. The pressure in the coronary sinus was increased from 5 to 25 torr by elevating the drainage reservoir in a stepwise fashion. Cardiac index, coronary arteriovenous difference, rate of rise of left ventricular pressure, left ventricular systolic time intervals, and coronary blood flow were measured. When the coronary sinus pressure reached 15 torr, there was a significant decrease in cardiac index (3.60 +/- 0.5 to 2.70 +/- 0.6 L/min/m2, p less than 0.001), coronary blood flow (13.7 +/- 3.1 to 7.0 +/- 2.1 ml/min, p less than 0.001), rate of rise of left ventricular pressure (1,567 +/- 275 to 1,331 +/- 314, p less than 0.05), and an increase in coronary arteriovenous difference (62.8% +/- 9.3% to 70.5% +/- 5.4% saturation, p less than 0.03). These experimental results were correlated with postoperative catheterization findings in 24 patients with the Fontan procedure. Patients with a mean right atrial pressure less than 15 torr had a left ventricular ejection fraction of 93% +/- 6% of predicted, whereas patients with a right atrial pressure of 15 torr or more had a left ventricular ejection fraction of 75% +/- 13% of predicted (p less than 0.001). These experimental and clinical data strongly suggest that elevated coronary sinus pressure has deleterious effects on ventricular function after the Fontan procedure. Modifications of the procedure, such as using the rudimentary right ventricle when feasible or diverting coronary sinus flow to the pulmonary venous atrium, might decrease coronary sinus hypertension and improve long-term results.

Halothane and Isoflurane Do Not Decrease Pao2 during One-Lung Ventilation in Intravenously Anesthetized Patients

We examined the effect of the inhalational anesthetics halothane (H) and isoflurane (IF) on arterial oxygenation during one-lung ventilation. Twenty consenting patients who required thoracotomy and one-lung ventilation were initially anesthetized only with the intravenous agents, diazepam, fentanyl, pancuronium, metocurine, and infusions of either ketamine or methohexital. A double lumen endotracheal tube was inserted, and each patient's lungs were mechanically ventilated (two-lung ventilation, step 1) with 100% O2 while the patient was in the lateral decubitus position. After the pleura was opened, the nondependent lung was collapsed while the dependent lung continued to be ventilated with 100% O2. After serial PaO2 measurements indicated achievement of stable one-lung ventilation conditions (step 2), intravenous anesthetic agents were discontinued, and either H (n = 10) or IF (n = 10) was administered (step 3) so that PETH = 7.70 +/- 0.61 mm Hg and PETIF = 9.89 +/- 1.08 mm Hg for more than 15 min; at the end of step 3, PaH/PETH = 0.82 (n = 5), PaIF/PETIF = 0.75 (n = 5), PvH/PETH = 0.64 (n = 3), and PvIF/PETIF = 0.68 (n = 3). The inhalational anesthetics were then discontinued, and intravenous agents were reinstituted, allowing PETH and PETIF to decrease below 0.50 mm Hg (step 4). Two-lung ventilation was resumed at the end of the surgical procedure (step 5). PaO2 decreased from 441 +/- 64 to 252 +/- 70 mm Hg when one-lung ventilation was achieved (steps 1-2), and PaO2 increased from 258 +/- 72 to 395 +/- 65 mm Hg when two-lung ventilation was resumed (steps 4-5).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of parathyroid hormone on myocardial energy metabolism in the rat

AbstractEffect of parathyroid hormone on myocardial energy metabolism in the rat. This study examined the effect of parathyroid hormone (PTH) on myocardial energy production, transfer, and utilization. Rats (150 to 200 g) were injected with 1-84 PTH, 200 U/day i.p., or 1-34 PTH, 200 or 300 U/day i.p., for 4 days. Control animals received the vehicle only. The effect of the simultaneous administration of calcium channel blocker, verapamil, was also examined. Myocardial contents of Pi, ATP, and CP were significantly (P<0.01) lower in the 1-84 PTH-treated rats than in control animals. Both 1-84 PTH and 1-34 significantly (P < 0.01) reduced mitochondrial oxygen consumption without altering ADP:0 ratio indicating reduced phosphorylation. 1-84 and 1-34 PTH significantly (P < 0.01) reduced the activities of mitochondrial and myofibrillar creatine phosphokinase and 1-84 PTH inhibited (P < 0.01) the activities of mitochondrial Mg ATPase and those of myofibrillar Ca ATPase. There were significant (P < 0.01) increments in myocardial45Ca and in total calcium content in 1-84 PTH-treated rats. Verapamil abolished all the effects of 1-84 PTH. Similarly, inactivation of 1-84 PTH abolished its effects. Treatment with 1-84 PTH for 10 days was associated with a significant decrease in cardiac index and mean arterial pressure. Our data demonstrate that both 1-84 and 1-34 PTH impair energy production, transfer, and utilization. These biochemical derangements, if maintained, produce a decrease in cardiac index. It appears that the enhanced entry and the accumulation of calcium in the myocardium, either directly and/or indirectly, are responsible for the action of PTH on energy metabolism of the heart.Effet de l'hormone parathyroïdienne sur le métabolisme énergétique myocardique chez le rat. Cette étude a examiné l'effet de l'hormone parathyroïdienne (PTH) sur la production, le transfert et l'utilisation de l'énergie myocardique. Des rats (150 à 200 g) ont reçu des injections de PTH 1–84, 200 U/jour i.p., ou de PTH 1–34, 200 ou 300/jour i.p., pendant 4 jours. Les animaux contrôles ont reçu le solvant seulement. L'effet de l'administration simultanée d'un bloqueur des canaux calciques, le vérapamil, a aussi été étudié. Le contenu myocardique en Pi, ATP, et CP était significativement (P < 0,01) moindre chez les animaux traités par la PTH 1–84 que chez les animaux contrôles. Les PTH 1–84 et 1–34 ont réduit chacune significativement (P < 0,01) la consommation mitochondriale d'oxygène sans altérer le rapport ADP:O, indiquant une phosphorylation réduite. Les PTH 1–84 et 1–34 ont significativement (P < 0,01) réduit les activités créatinine phosphokinases mitochondriale et myofibrillaire et al PTH 1–84a inhibé (P < 0,01) les activités Mg ATPase mitochondriale et Ça ATPase myofibrillaire. Il existait un accroissement significatif (P < 0,01) du contenu myocardique en45CA et en calcium total chez les rats traités par la PTH 1–84. Le vérapamil a aboli tous les effets de la PTH 1–84. De même, l'inactivation de la PTH 1–84a supprimé ses effets. Le traitement par la PTH 1–84 pendant 10 jours était associé avec une baisse significative de l'index cardiaque et de la pression artérielle moyenne. Nos données démontrent que les PTH 1–84 altèrent la production, le transfert, et l'utilisation d'énergie. Que ces anomalies biochimiques, si elles persistent, produisent une diminution de l'index cardiaque. Il apparaît que l'augmentation de l'entrée et l'accumulation de calcium dans le myocarde, directement et/ou indirectement, sont responsables de l'action de la PTH sur le métabolisme énergétique du coeur.

Adverse hemodynamic and clinical effects of calcium channel blockade in pulmonary hypertension secondary to obliterative pulmonary vascular disease

The hemodynamic and clinical responses to calcium channel blockade with verapamil and nifedipine were compared with those of hydralazine in 12 patients with pulmonary hypertension secondary to obliterative pulmonary vascular disease. All three drugs produced a marked and similar decrease in pulmonary vascular resistance; however, this was accompanied by a significant increase in cardiac index with hydralazine (+0.71 liter/min per m2, p less than 0.01), no change in cardiac index with nifedipine and a significant decrease in cardiac index with verapamil (-0.25 liter/min per m2, p less than 0.05). Mean pulmonary artery pressure decreased markedly with both calcium channel blocking drugs (-16.0 mm Hg with verapamil and -14.5 mm Hg with nifedipine, both p less than 0.01), but this was associated with a concomitant increase in mean right atrial pressure (+6.2 mm Hg with verapamil and +4.4 mm Hg with nifedipine, both p less than 0.01); neither variable changed after hydralazine. Hence, right ventricular performance (as reflected by right ventricular stroke work index) deteriorated during treatment with both calcium channel blocking drugs, despite the decrease in resistance to right ventricular ejection; in contrast, right ventricular stroke work index increased after hydralazine. The unfavorable hemodynamic effects of calcium channel blockade were accompanied by severe adverse clinical events, including profound hypotension and cardiogenic shock during acute drug administration and the exacerbation of right heart failure during long-term treatment. These deleterious responses to verapamil and nifedipine are likely the result of a direct depressant effect exerted by these drugs on right ventricular function independent of their pulmonary vasodilatory actions.

Effects of flecainide on ventricular function: Clinical and experimental correlations

Flecainide has unusual electrophysiologic properties and a high potency for the suppression of ventricular tachyarrhythmias. Little is known about its inotropic and hemodynamic actions. In isolated rabbit papillary muscle, it produced a concentration-dependent depression of contractile force, the threshold concentration being 1.0 μg/ml. In patients undergoing coronary angiography for ischemic heart disease and given 1 (n = 11) and 2 mg/kg (n = 11) of flecainide acetate i.v., there was no change in heart rate or mean arterial pressure. The vehicle in which i.v. flecainide was suspended had no significant effects in 6 patients in whom it was tested. Both doses produced comparable hemodynamic effects irrespective of the level of the left ventricular ejection fraction. The mean right atrial pressure increased by 12% (p < 0.05) after 1 mg/kg and by 15% (p < 0.01) after 2 mg/kg of the drug. The corresponding increases in mean wedge pressure were 44% (p < 0.05) and 33% (p < 0.05), in mean pulmonary artery pressure 27% (p < 0.01) and 28% (p < 0.05), in systemic vascular resistance 10% (p < 0.05) and 9% (not significant [NS]) and in pulmonary vascular resistance 6% (NS) and 49% (p < 0.05). Significant decreases in cardiac index (8 and 12%, p < 0.05), stroke volume index (11 and 15%, p < 0.01) and stroke work index (12%, p < 0.05, and 21%, p < 0.01) as well as in left ventricular ejection fraction (15 and 16%, p < 0.01) were also induced by the 2 doses of flecainide. In 373 patients (67 with a history of cardiac failure) given doses of flecainide to control ventricular tachyarrhythmias, heart failure developed or was aggravated in 16, an incidence of 4.3%. The overall data indicate that flecainide exhibits significant but modest negative inotropic effects that may become clinically significant in the subset of patients with compromised ventricular function. Its use in patients with severely depressed myocardial function warrants caution.

High-Dose Hydromorphone (Dilaudid) for Coronary Artery Bypass Surgery

The hemodynamic effects of high-dose hydromorphone hydrochloride (H), 1.25 mg/kg, were investigated in 10 patients with normal ventricular function undergoing coronary artery bypass graft (CABG) surgery. One patient with unstable angina was excluded from the study because of hypotension and facial flushing after a 6-mg test dose of H. Nine patients showed no significant change in heart rate (HR), mean arterial pressure (MAP), cardiac index (CI), left ventricular stroke work index (LVSWI), systemic vascular resistance (SVR), pulmonary capillary wedge pressure (PCWP), or coronary perfusion pressure (CPP) after H; central venous pressure (CVP) increased significantly (P less than 0.05). Loss of consciousness did not occur reliably after H. The addition of 50% N2O to H produced significant decreases in CI and LVSWI (P less than 0.05). Hemodynamic responses to tracheal intubation, skin incision, and sternotomy included depression of CI, elevation of SVR, and increased MAP (P less than 0.05). Vasodilators were required in eight patients before aortic cannulation and after extracorporeal circulation. Mean time to awakening was 7.6 hr after the full dose of H, and extubation was performed the morning after surgery (21 hr after H) according to our usual practice. We conclude that very large doses of H (equivalent in analgesic terms to 10 mg/kg of morphine sulfate) are well tolerated by most patients undergoing CABG surgery, but unconsciousness and complete suppression of sympathetic responses require supplementation of H with additional anesthetic agents or vasodilators.