LV Dpdt Research Articles

Comparative study of toborinone (OPC-18790) and milrinone on energy metabolism in microembolized guinea pig hearts

The effects of toborinone (OPC-18790) and milrinone on cardiac function and energetics were compared in microembolized guinea pig hearts. Male guinea pig hearts were perfused according to the Langendorff method and microembolization was induced by injecting microspheres. The hearts were then treated with toborinone (10 μM), milrinone (4 μM), and vehicle. Energy metabolism in hearts was assessed by 31-phosphorus magnetic resonance spectroscopy ( 31P-MRS). Microembolization produced a decrease in coronary perfusion flow (CPF), left ventricular developed pressure (LVP), and peak LVdP dt by about 50% concomitantly with a decrease in creatine phosphate (PCr) and ATP and an increase in inorganic phosphate (Pi) and Pi PCr ratio. Toborinone and milrinone increased peak LVdP dt , an index of contractility, by 15 ± 2% and 18 ± 3%, respectively. Milrinone increased heart rate (HR) by 22 ± 4% but toborinone did not change HR. Toborinone did not change PCr, ATP, Pi, Pi PCr , and intracellular pH (pHi) compared with the vehicle. On the other hand, milrinone decreased PCr and increased Pi and Pi PCr compared with toborinone or vehicle. These results suggest that the different effects between toborinone and milrinone on energy metabolism in microembolized hearts may be due to the difference of chronotropic action between these drugs. Thus toborinone, a positive inotropic agent without chronotropic action, may be effective in acute treatment of ischemic heart failure.

The protective effects of ischemic and calcitonin gene-related peptide-induced preconditioning on myocardial injury by endothelin-1 in the isolated perfused rat heart

This study was to investigate the effects of ischemic preconditioning on endothelin-1-induced myocardial injury and the role of calcitonin gene-related peptide (CGRP) played in such effects. The rat hearts were perfused in a Langendorff mode. Heart rates (HR), coronary flow (CF). left ventricular pressure (LVP) and its first derivative (LV dp dt max ) were recorded and creatinine phosphate kinase (CPK) from coronary effluent was measured. There were no changes in HR, CF, LVP, or LV dp dt max throughout the experiment in the control hearts. Endothelin-1 (100 pmol) significantly decreased HR and CF, impaired the cardiac function, and increased the CPK release. However, the HR, CF, LVP and LV dp dt max were significantly improved, while the CPK release was decreased in the preconditioned hearts. CGRP 8–37, a selective CGRP receptor antagonist, abolished the cardioprotection of ischemic preconditioning, such as the cardiac function and the CPK release. A similar cardioprotection was observed in the hearts pretreated with CGRP. However, the CGRP-induced preconditioning-like protection was abolished in the presence of CGRP 8–37or 1-(5-isoquinolinylsulfonyl) -2-methylpiperazine. an inhibitor of protein kinase C. The present study suggests that the cardioproteclive effect of ischemic preconditioning on endothelin-1-induced myocardial injury is mediated by CGRP, and that the cardioprotection of CGRP-induced preconditioning is related to the activation of protein kinase C.

Functional responses of the left and right heart of diabetic rats to α- and β-adrenergic receptor stimulation

It was the aim of the present study to examine the influence of α- and β-receptor stimulation on the function of the right (RV) and left (LV) ventricle of streptozotocin-diabetic rats (STZ; 60 mg · kg −1; n = 14). Phenylephrine (PE; 3 mg · kg −1 · h −1) or isoproterenol (ISO; 24 μg · kg −1 · h −1) were infused intravenously for 20 min 4 weeks after STZ injection. The hemodynamic parameters were measured on intact, anaesthetized animals with special Millar ® ultraminiature tipcatheter manometers. In the non-diabetic animals ( n = 15), PE caused a significant elevation of left ventricular systolic pressure (LVSP) from 138.5 ± 3.2 to 205.4 ± 7.5 mmHg and raised heart rate (HR) from 362 ± 12.6 to 399 ± 17.2 beats · min −1 (mean ± S.E.M.; P < 0.05). LVSP and HR were significantly lower in the diabetic animals under control conditions (110.5 ± 6.4 mmHg and 273 ± 16.0 beats · min −1, respectively) and not affected by PE. ISO induced a significant and comparable decrease in diastolic aortic pressure (DAP) and an increase in HR in both the non-diabetic and diabetic group. The PE-induced enhancements of LV dP dt max and RV dP dt max from 10533 ± 805 to 21533 ± 1386 and from 2044 ± 262 to 3867 ± 733 mmHg · s −1 were significant in the control animals. In the diabetic rats, LV dP dt max was lower (5971 ± 901 mmHg · s −1) and was increased by PE to the range of control rats (11171 ± 1591 mmHg · s −1. The PE-induced elevation of RV dP dt max from 2028 ± 284 to 2771 ± 391 mmHg · s −1 was less pronounced in the diabetic rats than in the controls. Under the influence of ISO, the increase of dP dt max in both ventricles was comparable to the effect of PE and fully preserved in the diabetic animals. Right ventricular systolic pressure (RVSP) was increased under PE and ISO in both groups to comparable values. These results demonstrate that the in vivo response to β-adrenoceptor stimulation is well preserved in the diabetic rat, while the effects of α-stimulation are markedly reduced, especially in the left ventricle and systemic circulation.

Evaluation of a new method using telemetry for monitoring the left ventricular pressure in free-moving rats

Left ventricular pressure (LVP) in free-moving rats was continuously measured for 2 weeks by a telemetry blood pressure measurement system. Prior to LVP measurement, a dummy transmitter was used to determine whether organ weights, including that of the heart and the lungs, or the stiffness of the left ventricular chamber were affected by the catheterization of the LV chamber. Organ weights did not increase, and no functional abnormalities were observed in the left ventricular pressure-volume relationship. The LVP transmitter was implanted in the left ventricle, and systolic LVP, end-diastolic LVP, LV dP dt max, and heart rate were measured. All parameters were essentially stable during the 2-week observation period after implantation, and the values, especially the heart rate, in the dark phase tended to be higher than those in the light phase. Microscopic examination of the left ventricular wall revealed that implantation of the dummy or LVP transmitter caused no histological damage. We confirmed that LVP in free-moving rats can be measured continuously for 2 weeks without any harmful effect on cardiac function and that this telemetry system should be useful in pharmacological and toxicological studies.

Effects of α-human atrial natriuretic peptide in guinea-pig isolated heart

The aim of the present investigation has been to ascertain whether or not atrial natriuretic peptides (ANP) can exert a direct effect on myocardial contractility. Alpha-human ANP (α-hANP) concentrations ranging from 1 pM to 50 nM have been used to perfuse guinea-pig isolated hearts in a non-recirculating Langendorff apparatus. A dual concentration-related effect has been induced by α-hANP on myocardial function. A maximal increase of +LV dP dt max (+56%; P < 0.001) has been observed when guinea-pig hearts were perfused with 100 pM α-hANP, whereas a 25% decrease ( P < 0.01) occurred with 50 nM α-hANP. Similar effects have also been induced by α-hANP on the coronary flow rate (CFR). A significant CFR increase (maximal at 10 pM α-hANP) was induced by picomolar concentrations of α-hANP, whereas a progressive decrease, which was maximal (−28%; P < 0.01) at 50 nM α-hANP, was observed with nanomolar concentrations of the peptide. No effects have been observed on heart rate. These results suggest that ANP has direct effects on both vascular and myocardial muscle cells. Coronary vasoconstriction induced by nanomolar concentrations of ANP can contribute to the cardiodepression, whereas ANP in picomolar concentrations can induce a coronary vasodilation which is not coupled with the enhanced myocardial contractility. The latter is the likely expression of a direct effect of the peptide on myocardial function.

EFFECTS OF ENDOTHELIN-1 ON ARTERIAL PRESSURE AND MYOCARDIAL CONTRACTILITY IN THE CONSCIOUS NORMOTENSIVE RABBIT

1. We studied the effects of an intravenous bolus of endothelin-1 on arterial pressure and myocardial contractility in the conscious rabbit. 2. Endothelin produced an initial fall in arterial pressure accompanied by an increase in heart rate. This was followed by a dose-dependent increase in arterial pressure, peaking about 7 min after injection, accompanied by a reciprocal fall in heart rate. 3. Left ventricular rate of change of pressure (LV dP dt) increased with endothelin except at higher doses (0.8 and 1.6 nmol/kg), where in some animals it decreased.

Effects of hemodynamic variables on myocardial K + balance during and after shortlasting ischemia

Ischemia-induced myocardial potassium loss and post-ischemic potassium reuptake was quantitated in 8 open chest pigs during control conditions and during hemodynamic alterations which have been shown to increase steady state sarcolemmal potassium fluxes. Myocardial K + balance was continuously computed before, during and after a 90 s occlusion of a branch of the circumflex artery during control (CTR), during pacing tachycardia (PACE: 34% increase in heart rate), during proximal aortic constriction (AC; 28% increase in LVSP), and during isoprenaline infusion (ISO; 135% increase in LVdP dt and 35% increase in heart rate). Ischemia-induced potassium loss increased significantly (40%) during ISO only. Higher basal metabolic rate, increased sarcolemmal K + conductance, or ischemia-induced depression of a more active Na K -pump during ISO are possible explanations to why increased K + loss appeared in this situation. The maximal rate of post-ischemic potassium reuptake was not different from CTR during PACE and ISO, but it was reduced during AC, which might be due to persisting subendocardial ischemia in early reperfusion when ventricular wall stress is high. The extent of potassium restoration was not different from CTR during AC, PACE and ISO.

Myocardial K + repletion and rise in contractility after brief ischemic periods in the pig

Potassium loss from the myocardium during brief ischemic periods is well documented, but whether intrinsic myocardial mechanisms restore this loss during reperfusion is unclear. To address this question, we established a shunt from the coronary sinus to the right atrium in seven open-chest pigs. Shunt flow and arterial and coronary sinus potassium concentrations were measured continuously in order to determine myocardial potassium balance. Thirty, 60 and 120 s occlusions of the mid-LAD coronary artery were repeated four times each at 10 min intervals with reproducible metabolic and hemodynamic responses. A myocardial K + reuptake amounting to 51 to 77% of K + release during ischemia occurred between 20 and 140 s of reperfusion. The maximal rate of K + reuptake was 1.4 (0.7 to 3.6), (median and 95% confidence interval), 4.3 (2.5 to 9.6) and 7.3 (4.9 to 13.4) μmol/100 g min after occlusion periods of 30, 60 and 120 s, respectively. Concomitant with the K + reuptake a progressive rise in LV dP dt occurred. Adrenoceptor stimulation could not explain these findings since catecholamine release declined during occlusion and reperfusion. We suggest that increased intracellular Na + concentration in early reperfusion stimulates the Na,K-pump and favours Ca ++ entry through Na + Ca ++ exchange, thereby mediating K + reuptake and the rise in contractility.

Naloxone requires circulating catecholamines to attenuate the cardiovascular suppression of endotoxic shock

The opiate antagonist naloxone (NAL) improves cardiovascular performance in canine hemorrhagic and endotoxic shock. If the release of neural and adrenal catecholamines is attenuated, NAL does not produce the expected improvement in cardiovascular function in canine hemorrhagic shock. This study tests the hypothesis that an endorphin-catecholamine interaction at the heart is responsible for a part of the cardiovascular depression of endotoxic shock. Two groups of five dogs were instrumented to measure mean arterial pressure (MAP), the first derivative of left ventricular pressure over time (LV dP dt max), cardiac output, and heart rate (HR); they were then subjected to bilateral adrenalectomy and given chlorisondamine to produce ganglionic blockade. At t = 0 min the dogs were given Escherichia coli endotoxin at 1 mg/kg (LD 80). Group I animals received NAL at 2 mg/kg + 2 mg/kg · hr iv from t = 30 to t = 60. At t = 45 these animals were treated with epinephrine (EPI) at 20 μg/kg · hr iv until t = 60. Group II animals got EPI from t = 30 to t = 60 and NAL from t = 45 to t = 60 at the same doses as Group I. In Group I, NAL alone had no effect on MAP, LV dP dt max, or HR. EPI significantly increased ( P < 0.002) cardiovascular parameters with MAP increasing from 52 ± 7 to 159 ± 14 mm Hg. In Group II, EPI produced a significant increase in all parameters, and the addition of NAL produced a further significant increase; MAP increased from 37 ± 3 to 126 ± 16 mm Hg with EPI and then to 175 ± 11 mm Hg with NAL. These data support the above hypothesis and indicate that circulating catecholamines need to be present to allow naloxone to reverse the cardiovascular depression in endotoxic shock.

Coronary flow reserve and diastolic dysfunction in hypertrophic cardiomyopathy

We studied 14 patients with hypertrophic cardiomyopathy during and after atrial pacing by simultaneous registration of left ventricular high fidelity pressure measurements and M-mode echocardiography together with great cardiac vein flow measured by thermodilution. Heart rate rose from 75 ± 18 to 142 ± 14 beats/minute with an increase of 93 ± 30 to 127 ± 46 milliliters/minute of great cardiac vein flow (increase 3f flow/beat: 0.8 versus 1.5 milliliters/beat in normal individuals; P < 0.05). In addition, diastolic hemodynamic parameters (such as left ventricular end-diastolic pressure, T 1 (time constant of relaxation) (of first 40 milliseconds) and T 2 (of second 40 milliseconds) and LVdP dt- ) changed from, respectively, 27.4 ± 7.1 to 24.0 ± 10.3 mm Hg; (NS), 67.3 ± 16.1 to 65.7 ± 22.2 liters/second; (NS) 68.6 ± 36.9 to 52.9 ± 19.4 ( P < 0.05), and 1592 ± 75 to 1302 ± 48 mm Hg/sec; P < 0.05. Left ventricular end-diastolic dimensions decreased whereas end-diastolic wall thickness increased from, respectively, 37 ± 3 to 34 ± 4 millimeters; ( P < 0.05) and 14 ± 2 to 17 ± 1 millimeters ( P < 0.05). Eleven of the 14 patients experienced angina pectoris concomitant with ST-T depression of 1 millimeter or more on the electro-cardiogram. No correlations were found between great cardiac venous flow and hemodynamically or ultrasonically derived diastolic parameters of left ventricular function.

Prevention of the "no reflow" phenomenon in the canine heart by mioflazine.

The effects of oral pretreatment with mioflazine (2.5 mg X kg-1) on regional myocardial reflow, infarct size reduction and hemodynamic recovery were studied in 24 anesthetized open-chest dogs undergoing 90 minutes of acute left anterior descending coronary artery (LAD) occlusion followed by 150 minutes of reperfusion. Regional myocardial blood flow was measured with tracer microspheres, and infarct size was determined by triphenyl tetrazolium chloride staining. Pretreatment with mioflazine resulted in a reduced diastolic aortic pressure (p less than 0.05) and an elevated cardiac output and LV dpdt max (p less than 0.05). These effects persisted throughout the experiment. In control animals (n = 12) a hyperemic reflow response was found in the perfusion area of the LAD during the first minutes of reperfusion. After 150 min of reperfusion, however, the viable myocardium of the LAD area became underperfused, and almost no reflow was found in the infarcted zones. In the animals pretreated with mioflazine (n = 12) the hyperemic response persisted throughout the reperfusion phase and the no-reflow phenomenon was prevented. Infarct size (expressed as percentage of perfusion area) tended to be smaller in this group: 23.7 +/- 12.4% versus 33.7 +/- 19.2% (p greater than 0.05). Left atrial pressure increased during LAD occlusion in both groups but normalized completely in the drug-pretreated animals (p less than 0.05). It is concluded that pretreatment with mioflazine prevents the no-reflow phenomenon after reperfusion of an evolving infarction, tends to reduce infarct size and improves hemodynamic recovery.

Observations on the relationship between digital heat loss and systemic hemodynamics in patients with heart disease

A concomitant study of finger heat discharge and systemic hemodynamics was undertaken in a series of 19 patients (mean age 54 years) suffering from various forms of heart disease. Finger heat discharge, as measured by calorimetry, was found to correlate significantly with mean circulation time (−0.760), cardiac index (+0.649), systemic vascular resistance (−0.615), stroke work index (+0.649), mean pulmonary artery pressure (−0.596), mean pulmonary capillary wedge pressure (−0.554), stroke index (+0.541), appearance time (−0.502) and mean right atrial pressure (−0.453). There was no significant correlation between finger heat discharge and mean arterial blood pressure, LV dp dt max , and heart rate. An effect of heart failure on finger heat discharge was found. When evidence of forward failure and also possibly backward failure was found, mean finger heat discharge was significantly diminished. When both forward and backward failure were present together, mean finger heat discharge fell still further.

Effect of coronary vasodilation on ventricular fibrillation threshold: Role of exogenous vasodilators and perfusion conditions

Even without myocardial ischemia, coronary blood flow (CBF) constitutes a major determinant of ventricular fibrillation threshold (VFT). To clarify whether abnormal distribution of normal or increased CBF plays any additional role, 14 open-chest chloralose-anesthetized dogs with fixednormalized heart rate, cardiac output, and systemic arterial pressure and separate servocontrolled left main coronary artery perfusion were studied as follows: VFT was determined first with coronary perfusion pressure (CPP) set at systemic level (80 mm Hg). Then CBF index was fixed at control levels (134.0 ± 9.5 ml/min · 100 gm −1 LV) and coronary vasodilation was induced by intracoronary infusion of adenosine until CPP decreased to 49.0 ± 2.0 mm Hg. Myocardial O 2 consumption, LV pressure, LV dp dt , and surface ECG remained unchanged. However, VFT decreased in all trials by about 45% ( p < 0.001). When CPP was reset to 80 mm Hg while maintaining vasodilation, CBF index increased by 90% to 255.4 ± 15.4 ml/min · 100 gm −1 LV and VFT by 26% ( p < 0.005) from control. Yet these VFT increases in response to intraluminal pharmacologic vasodilation were about 19% ( p < 0.002) lower than expected for similar CBF index increases occurring physiologically. We conclude that intraluminal coronary vasodilation not matched by appropriate CBF increase results in substantial decrease of VFT. Moreover, at comparable increase of CBF, spontaneous physiologic vasodilation is more effective than intraluminal pharmacologic coronary vasodilation in increasing VFT.

Experimental myocardial ischemia. III. Protective effect of glucose on myocardial function

Glucose has been long known as an important substrate for muscle cells and a number of laboratories have demonstrated that carbohydrate metabolism can contribute significantly to energy production both in aerobic and anerobic heart muscle. It has been suggested that these findings may have additional application in localized myocardial ischemic and infarction. Accordingly, experiments were performed to determine the effect of glucose on the mechanical and electrical activity of the heart. Left ventricular pressure (LVP), left ventricular dp dt ( LVdp dt , left ventricular end diastolic pressure (LVEDP), and the incidence of ventricular premature beats (VPB) and ventricular fibrillation (VF) were determined before and after ligation of the anterior descending coronary artery in three different canine heart experimental models. Thirty minutes after ligation of the left anterior descending coronary artery, the mean left ventricular pressure and mean left ventricular dp dt in the control group had decreased by 85 ± 6% and 74 ± 5% respectively. Under similar conditions glucose treatment produces an increase in left ventricular pressure and left ventricular dp dt of 111 ± 5% and 123 ± 8% respectively. The simultaneously measured mean left ventricular end diastolic pressure was 7.2 ± 0.9 ml for the control group and 3.7 ± 1 for the glucose treated group. Eighty-three percent of the control dogs developed ventricular ectopic activity. Fifty-eight percent of the control hearts developed ventricular fibrillation. In contrast, only 10% of the glucose treated hearts demonstrated ventricular ectopic activity and only 10% developed ventricular fibrillation. Glucose, as a bolus, consistently improved myocardial contractility and prevented ventricular fibrillation even after serum osmolality and serum glucose levels had returned to normal. These results demonstrate that glucose has a protective effect on the electrical and mechanical function of the canine heart during acute segmental myocardial ischemia. These findings may have application in the treatment of acute myocardial infarction in man.

Velocity of contractile element shortening in constrictive pericarditis and the effect of pulsus paradoxus

Force-velocity curves were constructed in nine patients with CP from a high-fidelity LV pressure tracing and its simultaneously recorded first derivative. V max and peak V ce (V pm) were calculated using the 2-element (Hill) or Voigt model; the curves were also constructed and V max measured using the 3-element Maxwell model. The measurements were compared with those in a group of four patients with CMO and with two control subjects. Measurements of the celerity of ventricular contraction-peak LVdp dt , Max dp/dt/IP and V max (2-element model)-were reduced in CP and greatly reduced in CMO. The effect of beat-to-beat variations in preload during pulsus paradoxus on the indices of ventricular celerity was studied. Peak LVdp dt and V pm varied with the change in LVEDP: the change in V max was negligible using the 2-element (Hill) or Voigt model. The 3-element (Maxwell) model failed to discriminate between the three groups of patients and seems to be invalid at high LV end-diastolic pressures.

The effect of noradrenaline on blood flow and oxygen consumption in normal and ischemic areas of myocardium

The effects of infusions of noradrenaline (1.0 μg/Kg./min.) were studied in dogs 2 to 3 hr. after acute ligation of the anterior descending branch of the left coronary artery. The model allowed blood flow to be simultaneously measured in the ischemic (infarcting) region and in the normal myocardium. Sampling blood from a local vein (draining the ischemic region) and from the coronary sinus (draining the normal myocardium) allowed comparisons to be made of oxygen consumption by the two regions. Coronary artery ligation resulted in a marked decrease in cardiac output and external cardiac work and an increase in left ventricular end-diastolic pressure with an unchanged LV dP dt . This is indicative of reduced myocardial contractility. Blood flow in the area supplied by the ligated vessel fell to a mean of 17.6 ± 2.7 ml./100 Gm./min., which is about 20 per cent of the normal flow in this region. Infusing noradrenaline 2 to 3 hr. after ligation increased systemic arterial pressure, LV dP dt max, external cardiac work, and blood flow and oxygen consumption in normal areas of the myocardium. There was some evidence that pulmonary shunting was increased by the drug. Noradrenaline also markedly increased peripheral coronary pressure and blood flow in the ischemic region, as assessed by 133Xenon clearance and by retrograde flow from the ligated vessel. Oxygen consumption in the ischemic region was also increased by noradrenaline. It is suggested that part of the increase in flow occurs in the endocardial region since the effective subendocardial perfusion pressure is increased by noradrenaline. This increase in flow would account for the reduction in infarct size which has been observed by other workers when the systemic arterial pressure is raised.

Left ventricular function in systole and diastole in constrictive pericarditis

Left ventricular function was studied in systole and diastole in 30 patients with constrictive pericarditis. Left ventricular end-diastolic volume was used to divide the patients into three arbitrary groups: severe constriction (EDV < 25 ml./M. 2), moderate constriction (EDV 25 to 50 ml./M. 2), and mild constriction (EDV > 50 ml./M. 2). The patients had high ventricular diastolic and venous filling pressures (mean LVEDP = 23 ± 7 mm. Hg, mean RVEDP = 20 ± 7 mm. Hg). Measurements related to absolute fiber shortening (stroke index, stroke work index, and left ventricular ejection rate) were reduced and linearly related to the degree of constriction as assessed by the end-diastolic volume. Measurements of relative fiber shortening or lengthening (ejection and filling fraction and circumferential fiber shortening) were normal despite great reduction in ventricular volumes. Velocity measurements, peak LV dp dt and mean velocity of circumferential fiber shortening were normal or slightly reduced. These changes were reflected in the systolic time interval measurements pre-ejection phase, left ventricular ejection time, and the ratio PEP LVET . Diastolic function of the ventricle was abnormal; the distensibility index of the ventriculo-pericardial system ( ΔV ΔP ) was low and the passive elastic modulus in-increased. The change in compliance correlated with the degree of constriction and there was a linear relationship between compliance and EDV. The ventricle was underloaded despite the high filling pressure and stroke work index was reduced; extrinsic compression raised the diastolic pressure and reduced left ventricular volumes.

The effects of massive doses of methylprednisolone on myocardial contractility and peripheral vascular resistance

Eleven normal dogs, nine chronically cardiac denervated dogs (four after betablockade with propranolol), and five acutely adrenalectomized and cardiac denervated dogs were studied on cardiopulmonary by-pass, at constant coronary blood flow, by means of an isovolumic left heart preparation. Methylprednisolone, in a dose of 30 mg. per kilogram of body weight, was given intravenously, and changes in myocardial contractility were assessed by measurement of left ventricular peak pressure (LVP max), peak LV dP dt , and maximum measured LV contractile element velocity (max V CE). In the normal dogs, methylprednisolone caused a significant enhancement of myocardial contractility (LVP max + 21 per cent), dP dt max + 27 per cent, and max V CE + 22 per cent, P < 0.01 in all). Chronically cardiac denervated animals showed similar effects, but with significantly greater percentage responses than the normal dogs in LVP max (+ 33 per cent) and dP dt max (+ 53 per cent), P < 0.01 in both. These changes were greatly attenuated or abolished in the denervated, beta-blocked dogs, and in the acutely adrenalectomized and cardiac denervated animals. These results confirm an acute, positive inotropic effect of methylprednisolone in vivo, and suggest that this influence is mediated indirectly by the release and/or potentiation of endogenous catecholamines.

The effects of dopamine on depressed myocardial function following coronary embolization in the closed-chest dog

Severe myocardial depression was induced in 12 anesthetized closed-chest dogs by mercury embolization of the left coronary artery and the effects of dopamine infusion (5 μg per kilogram per minute) studied. Coronary embolization produced decreases in cardiac output (CO) of 52 per cent, stroke volume (SV) of 49 per cent, left ventricular peak dP dt ( LVdP dt ) of 29 per cent, stroke work (SW) of 60 per per cent, LV systolic pressure (LVSP) of 14 per cent, and an increase in systemic vascular resistance (SVR) of 77 per cent. LV end-diastolic pressure (LVEDP) increased from 7 to 18 mm. Hg. After 20 minutes of dopamine, CO increased 30 per cent, SV 31 per cent, SW 46 per cent, LVdP dt 64 per cent, and LVSP 8 per cent; SVR decreased 18 per cent and LVEDP was 14 mm. Hg (all changes p < 0.05). Heart rate and mean aortic pressure did not change. After 60 minutes of dopamine, slight deterioration occurred but most parameters were still significantly improved. Thirty minutes after stopping dopamine, marked circulatory deterioration recurred. Persistent ventricular dysrhythmias occurred in 6 dogs, in 4 of whom dopamine dosage had to be decreased to 2.2 μg per kilogram per minute because of persistent ventricular tachycardia. It is concluded that dopamine will improve depressed myocardial function following acute coronary arterial embolization, at least temporarily, but that the incidence of serious ventricular dysrhythmias may well limit its use.

Assessment of quantitative apex cardiography: A noninvasive index of left ventricular function

Quantitative apex cardiography, a noninvasive method for assessment of left ventricular function, is based upon the close relation observed between the interval from the onset of ventricular depolarization to the preejection peak of the first derivative of the apex cardiogram ( R to dA dt ) and the interval from onset of ventricular depolarization to the peak of the first derivative of the left ventricular pressure pulse ( R to LV dP dt ). In 12 normal subjects R to dA dt varied directly with the R-R interval with a mean of 66 msec. A rate-corrected index, R to dA dt √RR , separated normal subjects (72 ± 12) from those with idiopathic hypertrophic subaortic stenosis (57 ± 15) or left ventricular failure (122 ± 23). When R to dA dt was compared with hemodynamic and angiographic indexes of left ventricular function in 23 patients studied at diagnostic cardiac catheterization, the following statistically significant correlations were obtained: Ejection fraction (r = −0.81), R to left ventricular dP dt ( r = +0.79), Vmax ( r = −0.62) , peak left ventricular dP dt ( r = −0.66) , left ventricular end-diastolic pressure (r = +0.49), and left ventricular end-diastolic volume (r = +0.64). These data support the use of quantitative apex cardiography for screening or serial clinical studies of left ventricular function.