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Measurement of hepatocellular function, cardiac output, effective blood volume, and oxygen saturation in rats.

The available techniques do not permit the measurement of hepatocellular function, cardiac output, effective blood volume, and oxygen saturation in small animals without the need of blood or tissue sampling. We present methodology that permits us to measure the above variables in the rat. Multiple doses of indocyanine green (ICG; 0.16-2.6 mg/kg) were given to pentobarbital-anesthetized rats, and [ICG] was continuously measured by an in vivo hemoreflectometer. Initial velocity of clearance (Vo) was determined from the [ICG] vs. time plot for each dose by nonlinear regression. The maximal velocity of clearance (Vmax; indicating hepatocellular function) was calculated. Vmax was 1) accurately determined using two, three, or four doses of ICG; 2) it was 1.09 +/- 0.16 mg.kg-1.min-1, not different from the Vo of the near-saturating dose of 25 mg/kg; and 3) it decreased after partial hepatectomy. Cardiac output was 41.89 +/- 1.46 ml.100 g-1.min-1, effective blood volume was 6.12 +/- 0.34 ml/100 g, and oxygen saturation was 92 +/- 2%. These methodologies may prove useful in the evaluation of hepatocellular dysfunction and hemodynamic parameters in the rat during and after various diseased states.

Animals↗

Depression of cardiac function after deep hypothermic circulatory arrest in deeply anesthetized neonatal lambs.

Cardiac dysfunction is common after neonatal cardiac operations. Previous in vivo studies in neonatal animal models however, have failed to demonstrate decreased left ventricular function after ischemia and reperfusion. Cardiac dysfunction may have been masked in these studies by increased endogenous catecholamine levels associated with the use of light halothane anesthesia. Currently, neonatal cardiac operations are often performed with deep opiate anesthesia, which suppresses catecholamine surges and may affect functional recovery. We therefore examined the recovery of left ventricular function after ischemia and reperfusion in neonatal lambs anesthetized with high-dose fentanyl citrate (450 micrograms/kg administered intravenously). Seven intact neonatal lambs with open-chest preparation were instrumented with left atrial and left ventricular pressure transducers, left ventricular dimension crystals, and a flow transducer. The lambs were cooled (< 18 degrees C) on cardiopulmonary bypass (22 +/- 6 minutes), exposed to deep hypothermic circulatory arrest (46 +/- 1 minutes), and rewarmed on cardiopulmonary bypass (30 +/- 10 minutes). Catecholamine levels and indexes of left ventricular function were determined before (baseline) and 30, 60, 120, 180, and 240 minutes after termination of cardiopulmonary bypass. Levels of epinephrine, norepinephrine, and dopamine were unchanged from baseline values. Left ventricular contractility (slope of end-systolic pressure-volume relationship) was depressed from baseline value (31.7 +/- 9.3 mm Hg/ml) at 30 minutes (15.7 +/- 6.4 mm Hg/ml) and 240 minutes (22.7 +/- 6.4 mm Hg/ml) but unchanged between 60 and 180 minutes. Left ventricular relaxation (time constant of isovolumic relaxation) was prolonged from baseline value (19.0 +/- 3.0 msec) at 30 minutes (31.4 +/- 10.0 msec) and 240 minutes (22.1 +/- 2.8 msec) but unchanged between 60 and 180 minutes. Afterload (left ventricular end-systolic meridional wall stress) was decreased at 30, 60, and 240 minutes. Indexes of global cardiac function (cardiac output, stroke volume), preload (end-diastolic volume), and left ventricular compliance (elastic constant of end-diastolic pressure-volume relationship) were unchanged from baseline values. In deeply anesthetized neonatal lambs exposed to ischemia and reperfusion, left ventricular contractility, relaxation, and afterload are markedly but transiently depressed early after reperfusion and mildly depressed late after reperfusion.

Animals↗

Evaluation of donor cardiac function for heart transplantation: experience of a French academic hospital.

OBJECTIVES: The diagnostic and therapeutic approaches for evaluation and management of cardiac function in brain-dead patients vary from country to country. The aim of the present study was to describe the results of the evaluation of brain-dead patients as potential cardiac donors in a French teaching hospital that manages the largest number of brain-dead patients in France. METHODS: Demographic parameters, the causes of brain death, clinical evolution, hemodynamic parameters, doses of inotropic and/or vasopressive drugs, the results of echocardiographic examination, and several biochemical markers of myocardial cell injury were retrospectively collected. RESULTS: Seventy-one consecutive brain-dead patients admitted to the intensive care unit of the Academic Hospital of Nancy from October 1st, 1998 to September 30, 1999 were analyzed. Twenty-nine patients were considered as potential heart donors: 22 males and 7 females aged 33 +/- 3 years (Mean + SEM). The cause of brain death was head trauma in 17 cases (59%), cerebrovascular disease in 10 cases (34%), and cerebral anoxia related to cardiac arrest in 2 cases (7%). Eighteen hearts (18/29 or 66%) were harvested and transplanted with a favorable outcome at one month in 17 cases. In 11 cases, the heart was not harvested, nine (9/29 or 31%) because of myocardial dysfunction upon subsequent echocardiographic examination and 2 because of the lack of matched recipients. CONCLUSION: Comparison of these results with those of other groups suggests that hormonal substitution with insulin and triiodothyronine in the presence of myocardial dysfunction could be of potential interest to correct myocardial dysfunction and increase the number of donor hearts.

Academic Medical Centers↗

[Modern techniques of assistance and mechanical replacement of cardiac function].

There has been intensive technological and clinical research for many years into the assistance and mechanical replacement of cardiac function. The simplest systems (extracorporeal circulation using centrifuge pumps, hemopump) and more complex systems (orthotopic or heterotopic pneumatic ventricles, electric ventricles) have been shown to be effective in a variety of situations which up to now could not be controlled by pharmacological methods. These situations are made amenable to improvement by the application of these techniques. They make it possible to await the recovery of autonomous function or, in its absence, transplantation. Experience over the past 30 years provides guidance for current research into the artificial heart.

Heart Diseases↗

Influence of pregnancy on mean systemic filling pressure and the cardiac function curve in guinea pigs.

To assess the degree of circulatory fullness and to evaluate the influence of peripheral and cardiac factors in the regulation of cardiac output during pregnancy, the following studies were conducted using pentobarbital-anesthetized, open-chest nonpregnant and late term pregnant guinea pigs. Mean circulatory filling pressure was taken as the equilibrium pressure when the pulmonary artery was constricted. Total vascular compliance was assessed by +/- 5-mL changes in blood volume performed while this constriction was maintained. A separate group of guinea pigs was prepared with a pulmonary artery electromagnetic flow probe and right atrial catheter. Rapid infusion of saline was used to increase right atrial pressure while the cardiac output was determined. Pregnancy was characterized by the following changes relative to nonpregnant controls: 51Cr-labelled RBC blood volume increased from 55 +/- 3 to 67 +/- 3 mL/kg; mean circulatory filling pressure increased from 7.1 +/- 0.2 to 8.0 +/- 0.5 mmHg (1 mmHg = 133.322 Pa); right atrial pressure decreased from 3.4 +/- 0.2 to 2.1 +/- 0.3 mmHg; and cardiac output increased from 71.8 +/- 3.9 to 96.8 +/- 3.3 mL.min-1.kg-1. Total vascular compliance was not changed (2.1 +/- 0.1 mL.kg-1.mmHg-1) and most of the expanded blood volume was accommodated as unstressed volume. The cardiac function curve was shifted upwards in pregnant animals. The resistance to venous return, as determined from the slope of the venous return curves, was not changed. These data suggest that the circulation of the pregnant guinea pig is slightly overfilled.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Effects of NaHCO3 on cardiac function and metabolism during hypoxic metabolic acidosis--2: Rapid infusion of NaHCO3].

The effects of 1M sodium bicarbonate (NaHCO3) on cardiac function and myocardial metabolism during hypoxia were compared with those of 1M sodium chloride (NaCl) in anesthetized dogs. Metabolic acidosis was induced with inhalation of low fraction of oxygen (9%) for 2 hours. NaHCO3 (n = 9) or NaCl (n = 10) was infused intravenously in a half dose of 0.2 x body weight x base excess mEq in 30 seconds. This treatment was repeated five minutes later. In NaHCO3 group; with first infusion, both blood and intramyocardial pH increased. Left ventricular pressure (LVP) and maximum rate of rise of LVP (LV dP/dt max) were unchanged. Cardiac index (CI) tended to increase, while left ventricular end-diastolic pressure (LVEDP) and LVEDP/LVP increased significantly. In five dogs in which myocardial glucose uptake increased, LV dP/dt max increased. With the second infusion, inspite of the increase of blood and intramyocardial pH, LVP and LV dP/dt max decreased significantly compared with the preceding values. In NaCl group, with first infusion, blood and intramyocardial pH decreased. CI increased significantly, while LVP and LV dP/dt max tended to decrease, and LVEDP and LVEDP/LVP increased significantly. After the second infusion, myocardial contractility was depressed significantly. In both groups, blood lactate (LA) level increased significantly, especially with NaHCO3 infusion. LV dP/dt max correlated significantly with LA in NaCl group (r = -0.614, P < 0.001). However, in NaHCO3 group, LV dP/dt max did not correlate with LA. Blood glucose level (r = 0.612, P < 0.001) and myocardial glucose uptake (r = 0.718, P < 0.001) correlated significantly with LV dP/dt max in NaHCO3 group.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Respiratory↗

Cardiac function predicts mortality following thoracoabdominal and descending thoracic aortic aneurysm repair.

OBJECTIVE: Previous studies have identified age, renal failure and aneurysm extent as predictors of mortality following thoracoabdominal and descending thoracic aortic aneurysm (TAA) repair. We studied the impact of coronary artery disease (CAD) and cardiac function on 30-day mortality following TAA repair. METHODS: Between February 1991 and May 2001, we performed 854 TAA repairs. Two hundred ninety-one patients (34%) had a history of coronary artery disease. One hundred forty-one/291 (49%) had undergone coronary artery bypass surgery (CAB) prior to TAA repair. We conducted multivariable analyses of known risk factors along with the left ventricular ejection fraction (EF) and prior CAB to determine the adjusted effect of CAD on outcome. RESULTS: Mortality in patients with CAD was 54/291 (18%) compared to 75/563 (13%) without CAD (P<0.05). In patients who had prior CAB, mortality was 31/141 (22%) compared to 98/713 (14%) patients without prior CAB, (P<0.02). In multivariable analysis, the effects of CAD and CAB on mortality were eliminated by consideration of a low EF (defined as less than 50%). CONCLUSION: Impaired left ventricular function appears to be the strongest cardiac predictor of mortality for TAA repair, independent of the presence of coronary artery disease or coronary artery bypass revascularization.

Adolescent↗

Changes during eating in oxygen consumption, cardiac function and body fluids of sheep.

1. A study was made of the changes taking place in O(2) consumption, cardiac function and the volume and composition of the body fluids of sheep while they consumed a meal of hay.2. During eating P(a, CO2) and P(v, CO2) both increased, pH decreased and free plasma [HCO(3) (-)] increased. Venous haematocrit increased sharply at the beginning of the meal, and declined slowly after feed was removed.3. Arterial P(O2) did not change significantly during eating. However P(v, O2) fell slightly but significantly. The O(2) saturation of venous blood fell due to the decline in pH. Estimated CO(2) in arterial blood increased as a consequence of increased haemoglobin content. The net effect was to increase arteriovenous difference in O(2) content from 4.4 ml./100 ml. before eating to 6.0 ml./100 ml. at the end of the meal.4. O(2) consumption increased about 60% during eating and fell rapidly thereafter. Heart rate followed a similar pattern. Cardiac output however increased only about 17%, from 6 to 7 l./min. Consequently stroke volume declined throughout the meal from 76 to 52 ml./beat.5. Plasma volume, estimated from measurements of T-1824, declined sharply by about 300 ml. at the beginning of the meal and recovered slowly after feed was removed. Blood volume declined less because of a rise in circulating erythrocytes.6. Extracellular fluid volume was estimated from measurements of thiocyanate and thiosulphate spaces. Thiocyanate space measurements were abandoned after thiocyanate was found to be concentrated in saliva. Considerable random variation occurred in measurements of changes in extracellular fluid from thiosulphate disappearance but the results did reveal a significant fall of 1000-1500 ml. in extracellular fluid volume during eating.7. The significance of these interrelated changes is discussed in relation to the maintenance of homoeostasis during eating in the sheep.

Animal Nutritional Physiological Phenomena↗

Limited predictive value of inducible sustained ventricular tachycardia for future occurrence of spontaneous ventricular tachycardia in patients with coronary artery disease and relatively preserved cardiac function.

To evaluate the significance of inducible sustained ventricular tachycardia (VT) in patients with coronary artery disease and relatively preserved cardiac function, 33 patients who met the following criteria were studied; documented nonsustained VT but no history of life-threatening arrhythmia, inducible sustained VT at electrophysiologic study, and implantation of a cardioverter-defibrillator. Eighteen patients developed clinical sustained VT within 2 years. By univariate analysis, left ventricular ejection fraction (EF) and the cycle length of induced VT were associated with clinical VT occurrence. By multivariate analysis, however, EF was the only independent predictor. Among 23 patients with EF 40% (P <.01). In coronary artery disease patients with relatively preserved EF, the incidence of clinical VT is considerably low even though sustained VT is inducible. Inducible VT is therefore not appropriate for risk stratification in this patient population.

Aged↗

[Cardiac function in isolated working rat heart with pressure overload hypertrophy: correlation with myocardial angiotensin II].

Using the isolated working rat heart model, we recorded cardiac function of the hypertrophied hearts induced by abdominal aortic banding and determined the myocardial angiotensin II level. Compared with the sham-operated control hearts, the maximal diastolic rate (-dp/dt) and coronary flow rate (per gram of left ventricular weight) were decreased, while the myocardial angiotensin II content was increased in the hypertrophied hearts. Correlation analysis revealed that both coronary flow rate (r = -0.8097, P < 0.001) and -dp/dt (r = -0.5463, P < 0.01) were negatively correlated to myocardial angiotensin II. We conclude that the activated cardiac renin-angiotensin system may be responsible for the decreased diastolic function and coronary reserve in the hypertrophied hearts.

Angiotensin II↗

Nitric oxide and cardiac function: ten years after, and continuing.

Nitric oxide (NO) is produced from virtually all cell types composing the myocardium and regulates cardiac function through both vascular-dependent and -independent effects. The former include regulation of coronary vessel tone, thrombogenicity, and proliferative and inflammatory properties as well as cellular cross-talk supporting angiogenesis. The latter comprise the direct effects of NO on several aspects of cardiomyocyte contractility, from the fine regulation of excitation-contraction coupling to modulation of (presynaptic and postsynaptic) autonomic signaling and mitochondrial respiration. This multifaceted involvement of NO in cardiac physiology is supported by a tight molecular regulation of the three NO synthases, from cellular spatial confinement to posttranslational allosteric modulation by specific interacting proteins, acting in concert to restrict the influence of NO to a particular intracellular target in a stimulus-specific manner. Loss of this specificity, such as produced on excessive NO delivery from inflammatory cells (or cytokine-stimulated cardiomyocytes themselves), may result in profound cellular disturbances leading to heart failure. Future therapeutic manipulations of cardiac NO synthesis will necessarily draw on additional characterization of the cellular and molecular determinants for the net effect of this versatile radical on the cardiomyocyte biology.

Animals↗

Cardiac function in adolescents and young adults with anorexia nervosa.

Twelve patients with anorexia nervosa (mean age 17.6 years) underwent noninvasive cardiac evaluation. All patients had normal sinus rhythm at rest, during exercise, and following 24-hr electrocardiographic monitoring. The chest roentgenograms demonstrated a small heart secondary to a loss of left ventricular mass. Three of four patients studied had left ventricular mass measurements less than 100 g (normal is 90-360 g). Most patients had an elevated heart rate response to exercise with a slightly blunted systolic and a normal diastolic blood pressure response. Eleven of the 12 patients had reduced overall maximal working capacity. All but one had normal left ventricular ejection fraction at rest. There was no evidence of arrhythmias at rest, during exercise, or with continuous electrocardiographic recording. Young patients with anorexia nervosa appeared to have essentially normal cardiac function with a reduction in left ventricular muscle mass.

Adolescent↗

Recovery of cardiac function by long-term left ventricular support in patients with end-stage cardiomyopathy.

Effects of long-term left ventricular (LV) support on end-stage cardiomyopathy patients is unclear. We applied our LV assist system (LVAS) to six heart transplant candidates, aged 17 to 49, with dilated cardiomyopathy, including one dilated phase hypertrophied cardiomyopathy. LVAS was installed between the left atrium and the ascending aorta, and the pump was positioned parecorporeally. In all patients, their general condition improved, and their pump flows were kept at 4 to 5 L/min. Exercise was started after stabilization of their general condition under constant pump flow. Natural heart size and function were examined by echocardiography. In the beginning of assist, all patients showed impaired cardiac function and LV dilation. During LV assist, systolic function measured by ejection time improved in all patients. Left ventricular end-diastolic dimension (LVDd), showed a remarkable decrease in two patients, who were weaned from LVAS after 3 months of support. They are doing well more than 1 year and 3 years after removal; peak VO2 levels (ml/min/kg) were 30 at 1.2 years and 27 at 2.7 years after removal. In the other four patients, however, LVDd had no remarkable changes, and three could not be weaned from LVAS. The last was discontinued from LVAS after 5 months of support because of infection and died 2 months after removal. From this experience, long-term LVAS may provide the chance for recovery of the natural heart in patients with end-stage cardiomyopathy. The patients whose hearts showed remodeling were able to be weaned from LVAS, and their heart function maintained in good condition for several years.

Adolescent↗

Cardiac function in open-chest dogs after left to right ventricular shunting and right coronary artery occlusion.

Patients with acquired ventricular septal defect (VSD) after myocardial infarction have a particularly bad prognosis if right ventricular function is severely impaired. The significance of an ischaemic right ventricular free wall on cardiac function during interventricular shunting was examined in open-chest dogs. An external interventricular shunt could be opened and closed at will, and by occlusion of the right coronary artery (RCA), a part of the right ventricular free wall was rendered ischaemic. Aortic flow decreased by 8 +/- 2% when the shunt was opened in the presence of a normal right ventricle, and by 16 +/- 2% (difference: P less than 0.05) in the presence of right ventricular ischaemia. Aortic flow fell by 19 +/- 3% when the RCA was occluded. Right ventricular dyskinesia was demonstrated after occlusion of RCA, by recording segment lengths in the right ventricular free wall. The dyskinesia was aggravated when the shunt was opened. The left ventricle exerted a 'negative' work on the ischaemic right ventricular free wall. Retention of blood in the right ventricle, with a subsequent decline in left ventricular filling and an almost unchanged interventricular shunting of blood, explain why aortic flow fell more when the shunt was opened in the presence of right ventricular ischaemia.

Animals↗

Influence of cardiac functional capacity on gender differences in maximal oxygen uptake in children.

OBJECTIVE: To examine the role of gender differences in cardiac functional capacity in explaining higher mean values for maximal oxygen uptake (VO(2)max) in boys than in girls. DESIGN: Comparative group exercise testing. SETTING: Pediatric exercise testing laboratory. SUBJECTS: Twenty-five prepubertal boys (mean [+/- SD] age, 12 +/- 0.4 years) and 24 premenarcheal girls (mean age, 11.7 +/- 0.5 years). INTERVENTIONS: Maximal incremental upright cycle exercise. MEASUREMENTS AND RESULTS: Mean values for VO(2)max were the following: boys, 47.2 +/- 6.1 mL/kg/min; and girls, 40.4 +/- 5.8 mL/kg/min (16.8% difference; p < 0.05). The average maximal stroke index with Doppler echocardiography was 62 +/- 9 mL/m(2) for boys and 55 +/- 9 mL/m(2) for girls (12.7% difference; p < 0.05). No significant gender differences were seen in maximal heart rate or arterial venous oxygen difference. When VO(2)max and maximal stroke volume (SV) were expressed relative to lean body mass, gender differences declined but persisted, falling to 6.2% and 5.2%, respectively. CONCLUSIONS: These findings indicate that differences in SV as well as in body composition contribute to gender-related variations in VO(2)max during childhood. Whether this reflects small gender differences in relative heart size or dynamic factors influencing ventricular preload and contractility during exercise is unknown.

Body Composition↗

Effects of thiopental and ketamine on cardiac function during moderate hemorrhage in chronically instrumented rats.

This study was designed to assess the effects of thiopental and ketamine on cardiac function after a blood loss of 2 ml/100 g of body weight. In nine Sprague-Dawley rats, a catheter was placed in the abdominal aorta, a pulsed Doppler probe was positioned around the thoracic aorta, and a wall-thickness probe was sutured onto the left ventricle. On three occasions, all rats were studied awake, during thiopental anesthesia, and during ketamine anesthesia. In awake rats, a 30% blood loss resulted in an immediate, transient hypotension (49%) and a prolonged decrease in cardiac output (39%) and stroke volume (28%). No significant changes were observed in the wall-thickening fraction, which is an index of cardiac contractility, and in the heart rate. The effect of thiopental on cardiovascular responses to moderate hemorrhage was minimal. Although ketamine did not affect the hypotensive response to moderate hemorrhage, it did accentuate systemic vasoconstriction and cardiac depression as indicated by a decrease in cardiac output (57%), stroke volume (49%), and wall thickness (47%).

Animals↗

Does balloon mitral valvuloplasty improve cardiac function? A mechanistic investigation into impact on exercise capacity.

Procedural technical success of balloon mitral valvuloplasty (BMV) is indicated by an increase in valve area and a reduction in transvalvar gradient, but there are conflicting results regarding whether these indicators correlate with subsequent improvements in exercise capacity. We conducted a study to explore the effects of valvuloplasty on cardiac function to gain insight into the mechanisms responsible for the impact on exercise ability. Sixteen patients with mitral stenosis participated in the study and the five who did not proceed to valvuloplasty served as the control group. All patients performed maximal cardiopulmonary exercise tests before and 6 weeks after valvuloplasty (without valvuloplasty in controls). Central haemodynamics including cardiac output were measured non-invasively at rest and peak exercise. At baseline, the cardiopulmonary exercise test results were similar in the two groups. Following valvuloplasty, cardiac output did not alter at rest, but increased significantly at peak exercise (8.7+/-1.7 to 10.5+/-2.1 l min(-1), P<0.01), as did peak cardiac power output (1.88+/-0.55 to 2.28+/-0.74, P<0.05) and cardiac reserve (1.07+/-0.33 to 1.45+/-0.55 watts, P<0.05). Aerobic exercise capacity improved (13.9+/-4.2 to 16.4+/-4.3 ml kg(-1) min(-1), P<0.01) as did exercise duration (354+/-270 to 500+/-266 s, P<0.01). There were no significant changes in the controls. There was a significant correlation between the changes in peak VO(2) and changes in cardiac reserve (r=0.62, P<0.01) but not with changes in resting haemodynamics. These changes did not correlate with changes in peri-procedural mitral valve haemodynamics, despite increases in mitral valve area from 1.05+/-0.16 to 1.74+/-0.4 cm(2) (P<0.0001), accompanied by falls in the transvalvar gradient and pulmonary artery pressure (12.4+/-4.7 to 4.5+/-3 mmHg, and 26.8+/-8.4 to 17.4+/-5.2 mmHg, respectively, all P<0.0001). In conclusion, we found that successful mitral valvuloplasty in our patient cohort led to improved cardiac and physical functional capacity but not resting haemodynamics. Neither indicators of technical success nor resting haemodynamics were very reliable in predicting functional improvement.

Adult↗

Differential effects of OPC-18790, amrinone and dobutamine on cardiac function and energy metabolism in the guinea-pig isolated ischaemic heart.

1. The effects of OPC-18790, a novel positive inotropic agent, on cardiac function and myocardial energy metabolism in the guinea-pig isolated heart with ischaemia were studied by 31P-magnetic resonance spectroscopy (MRS) and compared with those of amrinone and dobutamine. 2. Cardiac ischaemia was induced by intracoronary infusion of 15 microns microspheres to reduce coronary perfusion flow (CPF) by 50%. Microsphere embolisation caused a 40% decrease in left ventricular systolic pressure (LVSP), cardiac contractility measured by peak of ventricular pressure development (LVdP/dt) and slightly reduced heart rate. There was also a decrease in ATP and creatine phosphate (PCr) by 20%, an increase in inorganic phosphate (Pi) by 25% and an acidic shift of intracellular pH in the ischaemic heart. 3. In the ischaemic heart, OPC-18790, amrinone and dobutamine were applied at concentrations which increased LVdP/dt by about 60%. These compounds increased LVP by 15% to 30% and increased CPF by about 10%. Amrinone and dobutamine but not OPC-18790 increased heart rate. When these drugs produced the haemodynamic changes described above, amrinone and dobutamine reduced ATP and PCr, increased Pi and produced further intracellular acidosis, whereas, OPC-18790 did not change these parameters. 4. Cardiac pacing at 285 beats min-1 produced decreases in LVP, LVdP/dt and CPF by about 30%, 20%, 5%, respectively and an increase in Pi, decreases in PCr and ATP, and intracellular acidosis. 5. These results suggest that degradation of high energy phosphate compounds closely relates to increase in heart rate in the ischaemic heart. Positive inotropic agents without chronotropic action seem to be beneficial in support of the ischaemic heart.

Adenosine Triphosphate↗