Biomedical subjects

J Wikman-Coffelt

Publications and source records attributed to J Wikman-Coffelt.

At least 19 recordsLinked to original sources

PubMed1992

Intracellular calcium during pacing-induced ventricular fibrillation. Effects of lidocaine.

Hemodynamics and endocardial [Ca2+]i transients were studied during ventricular fibrillation in isolated perfused rat hearts. During 1 minute of pacing-induced ventricular fibrillation, the diastolic fibrillatory [Ca2+]i level increased significantly (p less than 0.001) above the end-systolic [Ca2+]i concentration of the last regular contraction. A bolus of lidocaine led to a decrease in the [Ca2+]i level during fibrillation (p less than 0.007) to the end-diastolic level of baseline conditions and then subsequently converted the heart to sinus rhythm. In 13 (62%) of the 21 studies described, post-lidocaine ventricular fibrillation converted to a brief period of asystole followed by sinus rhythm; in 8 (38%) of the studies, post-lidocaine ventricular fibrillation switched to ventricular tachycardia. Postfibrillatory cardiac dysfunction was related to the duration and degree of elevated diastolic [Ca2+]i. The authors conclude that [Ca2+]i levels are increased during ventricular fibrillation, and that lidocaine treatment leads to a prompt decrease in [Ca2+]i preceding conversion to sinus rhythm.

Animals↗

PubMed1992

Relationship between cytosolic calcium and oxygen consumption in isolated rat hearts.

Maximum oxygen consumption was attained in isolated perfused rat hearts using high perfusate calcium and/or isoproterenol, or phenylephrine. The amplitude of calcium transients was directly related to oxygen consumption until oxygen consumed per beat reached maximum. At saturating oxygen consumption the amplitude of [Ca2+]i transients continued to increase, indicative of a calcium overload. In all cases +dP/dt correlated proportionately with +dCa2+/dt. Augmented developed pressure, related to isoproterenol-induced increase in cytosolic cAMP, cannot be attributed totally to elevated levels of [Ca2+]i transients. Adenosine (10(-5) M) added to the medium containing isoproterenol (10(-6) M) negated the isoproterenol-induced increase in cAMP and returned cardiac performance, oxygen consumption, and amplitude of [Ca2+]i transients to control state.

Adenosine Triphosphate↗

PubMed1992

Effects of propafenone on pacing-induced ventricular fibrillation and intracellular calcium in rat hearts.

Propafenone is an antiarrhythmic agent with fast sodium channel, calcium channel, and beta-adrenergic receptor blocking properties. The effects of propafenone on arrhythmias, free intracellular calcium and left ventricular performance were studied using perfused rat hearts during (i) pacing-induced ventricular fibrillation and (ii) infusion with 2.65 x 10(-6) M, 5.3 x 10(-6) M and 7.9 x 10(-6) M propafenone hydrochloride (corresponding to approximately 1, 2 and 3 mg kg-1 body weight). A bolus of 1 mg kg-1 propafenone during ventricular fibrillation resulted in a decrease in intracellular calcium, with subsequent conversion to sinus rhythm. In perfused hearts with sinus rhythm propafenone produced a dose-dependent decrease in heart rate and myocardial oxygen consumption together with a rise in left ventricular diastolic pressure, and diastolic [Ca2+]i, indicative of depression of left ventricular function. We conclude that a bolus of propafenone during ventricular fibrillation leads to a decrease in [Ca2+]i preceding conversion to sinus rhythm. In rat hearts with sinus rhythm the depressive effects of propafenone on [Ca2+]i are dose dependent.

Animals↗

PubMed1992

Activation of glycolysis with isoproterenol but not digoxin reverses chronic alcohol depression in hamster hearts.

The purpose of this study was to confirm that an agent, which increases diastolic [Ca2+]i, namely digoxin, depresses cardiac performance, mitochondrial activity, and glycolysis in chronic alcohol-treated and myopathic hearts, and that an agent, which lowers diastolic [Ca2+]i, namely isoproterenol, activates cardiac performance, mitochondrial activity, and glycolysis in these animals. Energy levels, glycolysis, mitochondrial activity, hemodynamics, and cAMP were studied in isolated hearts from three groups of animals, i.e., 9-month control hamsters, hamsters given 50% alcohol until 9 months of age, and 6-month-old cardiomyopathic hamsters in heart failure. Isolated hearts were perfused with either a control medium, a medium containing isoproterenol, digoxin, or digoxin + isoproterenol. Measurement of phosphomonoester sugars, and glucose-6-phosphate, were used to assess glycolytic activity. Oxygen consumption was used to analyze mitochondrial activity. All hearts perfused with either isoproterenol or isoproterenol + digoxin showed an increase in developed pressure, rate-pressure-product, and a decrease in end-diastolic pressure. Isoproterenol activated mitochondrial activity and glycolysis in hearts from myopathic and chronic alcohol hamsters. Based on 31P-NMR studies, isoproterenol or isoproterenol + digoxin improved the over-all energy state of hearts from cardiomyopathic hamsters, but not hearts from control and chronic alcohol hamsters. Digoxin alone augmented the rate-pressure-product and oxygen consumption in control hearts but not hearts from myopathic and chronic alcohol hamsters. Digoxin caused an increase in end-diastolic pressure in myopathic and chronic alcohol hearts but not control hearts. Digoxin depressed glycolysis and worsened the energy state in hearts from cardiomyopathic and chronic alcohol hamsters, but not hearts from control hamsters. In conclusion digoxin, but not isoproterenol nor isoproterenol + digoxin, depressed cardiac performance and glycolysis as well as high energy phosphates in cardiomyopathic and chronic alcohol hearts. Isoproterenol added to digoxin negated the adverse effects of digoxin in cardiomyopathic and chronic alcohol hearts.

Animals↗

PubMed1991

Angiotensin II and phorbol esters depress cardiac performance and decrease diastolic and systolic [Ca2+]i in isolated perfused rat hearts.

Both angiotensin II and the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), significantly depressed developed pressure, oxygen consumption, and coronary flow in isolated perfused rat hearts and caused a decrease in diastolic and systolic [Ca2+]i and [Ca2+]i transients. PMA and angiotensin II did not change the levels of cAMP but moderately decreased PCr/Cr. The decrease in systolic [Ca2+]i and amplitude of [Ca2+]i transients caused by PMA and angiotensin II resulted in depressed cardiac function. Hearts perfused with PMA and angiotensin II had a decreased sensitivity to extracellular calcium. Depressed developed pressure and oxygen consumption in the PMA- and angiotensin II-treated hearts may have been due to a decrease in amplitude of effective [Ca2+]i transients, because the [Ca2+]i threshold for cross-bridge interaction was presumably higher than the diastolic [Ca2+]i in these hearts.

Angiotensin II↗

PubMed1991

Mechanism for depressed cardiac function in left ventricular volume overload.

To assess the effects of left ventricular chamber volume on the mechanism of changes in left ventricular developed pressure we performed phosphorous-31 nuclear magnetic resonance spectroscopy, hydrogen-1 nuclear magnetic resonance spectroscopy with a shift reagent, two-dimensional echocardiography, atomic absorption spectrophotometry, microsphere analysis, and surface fluorometry on isovolumic isolated perfused rat hearts with incremental intraventricular balloon volumes, while left ventricular pressure was concurrently monitored. A three-phasic response of developed pressure was noted: 0 to 100 microliters balloon volumes resulted in an increase in developed pressure, whereas developed pressure remained constant at 250 microliters and fell at 400 microliters. Oxygen consumption and [Ca2+]i transients followed the same pattern as developed pressure and coronary flow. Intraventricular volumes of 250 microliters or greater (a volume overload) caused endocardial ischemia, a greater decrease in extracellular versus intracellular water, thinning of the left ventricular free wall, and an increase in chamber size. Mechanical pressure on the tissue, induced by the volume overload, caused ischemia as further evidenced by (1) a negative effect on developed pressure, (2) a decrease in [Ca2+]i transients, (3) a [Ca2+]i overload, (4) a moderate decrease in the phosphorylation potential, and (5) an increase in the oxidation-reduction state (nicotinamide-adenine dinucleotide). The high intracellular calcium associated with volume overload may have been due to both compression and ischemia, which leads to an increased number of cross-bridges in rigor, a high end-diastolic pressure, and an increase in wall stress.

Animals↗

PubMed1991

Cardiac function and metabolism after chronic alcohol consumption: adaptation, reversibility, and effects of verapamil.

Hamsters were fed 50% alcohol instead of drinking water for up to 42 weeks (average serum alcohol levels were 0.12 +/- 0.06 gm/dl during the 42 weeks). One group of hamsters (28 weeks) was given verapamil 3 days before they were killed. Two groups were withdrawn from alcohol acutely (3 days before they were killed) at 14 and 28 weeks. High-energy phosphate compounds were studied in isolated hearts with 31P-MRS standardized by freeze clamping the tissue. Hemodynamics of the heart were monitored throughout the study. After 7 and 14 weeks of alcohol ingestion, developed pressure and the phosphorylation potential were depressed in the hearts of chronically treated hamsters. At 28 and 42 weeks developed pressure increased but was significantly below baseline values; however, the phosphorylation potential and [pH]i returned to baseline values at 28 and 42 weeks. Throughout the 7 to 42 weeks of alcohol ingestion the alcohol-treated hamsters had a significantly higher end-diastolic pressure as compared with control animals. Withdrawal of alcohol (3 days before the hamsters were killed) reversed the depression of developed pressure and the phosphorylation potential. Acute administration of verapamil (therapeutic dose 3 days before they were killed) to hamsters given alcohol for 28 weeks reversed the depressed hemodynamic values. Overall the data suggest an adaptation of the heart to continuing alcohol consumption, which was related to normalization of the phosphorylation potential and [pH]i and partial alleviation of functional depression.

Alcoholism↗

PubMed1991

Intracellular endocardial calcium and myocardial function in rat hearts.

Analyses of [Ca2+]i in the isolated beating rat heart (using Indo-1 dye) demonstrated a direct relationship between developed pressure and each of the following: (a) systolic [Ca2+]i; (b) amplitude of [Ca2+]i transients; and (c) diastolic level of [Ca2+]i. Agents which increased cAMP levels, augmented amplitude of [Ca2+]i transients, and lowered the resting level of [Ca2+]i, thereby shifting the relationship between developed pressure and diastolic as well as systolic [Ca2+]i concentrations towards lower [Ca2+]i levels for comparable peak systolic pressure measurements at constant end-diastolic pressure. Addition of adenosine to the perfusate containing isoproterenol completely prevented any cAMP-induced cytosolic changes. Interventions which altered [Ca2+]i and developed pressure, but did not increase cAMP (e.g., perfusion pressure, extracellular calcium, calcium entry blockers, and alpha agonist), caused an increase in diastolic levels of [Ca2+]i commensurate with the augmentation in developed pressure and amplitude of [Ca2+]i transients. When the diastolic [Ca2+]i rose to 400 nmoles and the cAMP was below 4 nmoles the heart fibrillated. The heart fibrillated at a diastolic [Ca2+]i of 350 nmoles when the cAMP was elevated to 6 nmoles. The diastolic level of [Ca2+]i at which the heart begins to fibrillate is indicative of the effect contraction threshold.

Adenosine↗

PubMed1991

[Ca2+]i transients in the cardiomyopathic hamster heart.

Intracellular [Ca2+] transients were studied in isolated hearts of healthy and cardiomyopathic hamsters in late failure perfused with glucose or pyruvate. Hearts of healthy hamsters developed similar pressures when perfused with either glucose or pyruvate, and [Ca2+]i transients were comparable in amplitude when perfused with either substrate. On the other hand, hearts of cardiomyopathic hamsters in late failure developed normal pressure when perfused with pyruvate but developed depressed pressure (50%) when perfused with glucose. The amplitude of [Ca2+]i transients fell severely and was associated with a high diastolic [Ca2+]i in cardiomyopathic hamster hearts when the perfusate was switched from pyruvate to glucose. The high phosphomonoester sugars as evidenced by 31P nuclear magnetic resonance studies and the depressed oxygen consumption in the cardiomyopathic hamster hearts perfused with glucose reflect an inhibition in glycolysis and a subsequent decrease in mitochondrial activity. Without an adequate delivery of substrate to the mitochondria in the cardiomyopathic hamster, the myocardium is no longer capable of maintaining its [Ca2+]i homeostasis.

Animals↗

PubMed1991

Protective effects of calcium antagonists on energy and substrate metabolism during ischemia and reperfusion in hypertensive myocardial hypertrophy.

The aim of the present study was to define the protective effects of verapamil and nifedipine on mechanical performance and energy and substrate metabolism of the postischemically reperfused myocardium in a chronic pressure overload cardiac hypertrophy model. The isolated beating rat heart preparation was used and left ventricular pressures and high-energy phosphates were continuously monitored during 30 min of global ischemia and reperfusion, respectively. Recovery of mechanical performance and high-energy phosphate and sugar monophosphate metabolism was significantly impaired in untreated hypertrophied hearts compared with normal control hearts and hypertrophied hearts treated with calcium antagonists. In hypertrophied hearts with chronic verapamil treatment, recovery was significantly improved compared to acute verapamil treatment, nifedipine treatment, and normal control hearts. Thus, verapamil and nifedipine exerted a protective effect on the postischemic recovery of the hypertrophied myocardium that was most prominent following long-term pretreatment with verapamil. Prolonged maintenance of adequate plasma levels and tissue distribution of calcium antagonists before an ischemic event may improve the postischemic prognosis in the presence of pressure-induced myocardial hypertrophy.

Adenosine Triphosphate↗

PubMed1991

Alcohol and pyruvate cardioplegia. Twenty-four-hour in situ preservation of hamster hearts.

Isolated hamster hearts were first perfused with a normal Krebs-Henseleit medium to demonstrate comparable viability of hearts before perfusing and storing them for 24 hours in one of three solutions. The three solutions were a physiologic saline with pyruvate as the substrate and 4% alcohol to arrest the heart (group 1), a standard cardioplegic solution (group 2), and an alcohol-free physiologic saline with pyruvate as the substrate (group 3). Recovery in terms of rate/pressure product and oxygen consumption after 30 minutes of reperfusion was 81% and 93%, respectively, for group 1, 13% and 32% for group 2, and 70% and 72% for group 3. Percent of physiologic recovery was not related to recovery of adenosine triphosphate. The adenosine triphosphate level returned to approximately 40% control level in all three groups, and in all three groups inorganic phosphate remained approximately 320% over control level after 30 minutes of reperfusion. Phosphocreatine level significantly higher in groups 1 and 3 than in group 2, as a result of improved oxygen consumption. Intracellular pH, determined by phosphorous 31 nuclear magnetic resonance spectroscopy, was physiologic in groups 1 and 3 but alkaline in group 2. This alkalinity may have been caused by leaky membranes. Pyruvate helped preserve mitochondrial function during depressed oxygen delivery, such as was seen during the 24-hour storage period. Four percent alcohol arrested the heart; combined with pyruvate plus alcohol solution were better than a standard cardioplegic solution for maintaining functional capability.

Animals↗

PubMed1990

Calcium-dependent fluorescence transients during ventricular fibrillation.

Using surface fluorometry, calcium-dependent fluorescence transients were recorded during ventricular fibrillation in perfused rat and hamster hearts loaded with INDO 1-AM (fluorimetric reagent for calcium ion). Among a series of 203 consecutive isolated heart studies, 13 instances of ventricular fibrillation occurred. These arrhythmias developed during pretreatment with isoproterenol, dobutamine, norepinephrine, phenylephrine, digoxin, and 4 mmol/L calcium in the perfusate. Alternans behavior of calcium transients occurred in three cases; premature beats preceded ventricular fibrillation in six cases. Premature beats led to a further increase in the free intracellular calcium ([Ca2+]i) concentration, resulting in a stronger contraction with the subsequent beat and/or the initiation of ventricular fibrillation. Two distinct patterns of calcium transients were seen: ventricular fibrillation type 1 showed fast disorganized transients with small amplitude and an irregular, nonuniform tracing; type 2 revealed fast activity and multiform, polymorphous transients with marked changes in amplitude. Independent of the morphologic type of fibrillation, [Ca2+]i remained constant or even increased during an observation time up to 9 minutes. No intracellular hypocalcemia was observed. Isoproterenol pretreatment resulted in [Ca2+]i levels in the range of the end-diastolic calcium level of the last regular contraction. Fibrillating calcium transients after norepinephrine, dobutamine, phenylephrine, digoxin, high calcium, and fast pacing were in the previous end-systolic range. It is suggested that inotropic agents acting without a major elevation of cyclic adenosine monophosphate result in higher [Ca2+]i.

Animals↗

PubMed1990

Ethanol protects the heart against the calcium paradox injury.

Rat hearts were depleted of Ca2+ (less than 10(-9) M) for 10 min, followed by 15 min of Ca2+-repletion. The calcium paradox injury occurs during Ca2+-repletion, after a period of calcium depletion. The calcium paradox injury was assessed by percent recovery (hemodynamics, [Ca2+]i, and energy levels) during Ca2+-repletion. A decrease in Na+ concentration during Ca2(+)-depletion did not allow for recovery during Ca2(+)-repletion, however 2.5% and 5% ethanol during Ca2(+)-depletion allowed for an approximate 50% recovery during Ca2(+)-repletion. A combination of ethanol (2.5% or 5%) with a low extracellular Na+ concentration (88 mM) allowed for complete recovery. Ethanol prevented a depletion of diastolic [Ca2+]i during Ca2(+)-depletion, and allowed for a return of normal diastolic [Ca2+]i during Ca2(+)-repletion. Ethanol modulates the activity of the Na+/Ca2+ exchanger and protects against the Ca2(+)-paradox injury.

Animals↗

PubMed1990

31P magnetic resonance spectroscopy of pressure overload hypertrophy in rats: effect of reduced perfusion pressure.

STUDY OBJECTIVE - The purpose of the study was to confirm the presence of abnormalities in the coronary vessels of hypertensive hearts, and to examine the effects of reduced coronary perfusion pressure. DESIGN - Rats were made hypertensive by aortic banding, after which coronary flow and myocardial energy metabolites were studied in isolated hearts at physiological (140 cm H2O) and reduced (80 cm H2O) coronary perfusion pressures and compared with normotensive controls. SUBJECTS - Wistar-Kyoto rats between 250 and 300 g were used. Left ventricular hypertrophy was generated by aortic banding in 29 rats; 8 were studied one week after banding, and 21 three weeks after banding. There were 45 controls. MEASUREMENTS and RESULTS - Energy metabolites were assessed using 31P magnetic resonance spectroscopy, standardised by high performance liquid chromatography of rapidly freeze clamped tissue. Left ventricular wall thickness was determined using two dimensional echocardiography. Coronary flow (normalised for heart weight) was reduced significantly after one and three weeks of left ventricular hypertrophy, and at either physiological or below physiological pressures. Hearts from aortic banded animals developed higher intraventricular pressure with reduced oxygen consumption when perfused at a physiological pressure, indicating increased thermodynamic efficiency. When perfused at reduced pressure, the developed pressure declined significantly in both the one week and the three week banded groups compared to normal hearts. The phosphorylation potential and intracellular pH (pHi) were not significantly lower after one week and three weeks of left ventricular hypertrophy when perfused at physiological pressure. When perfused at reduced pressure, phosphorylation potential declined significantly in both groups of hypertrophied hearts, whereas pHi declined significantly only in the three week hypertrophy group. CONCLUSIONS - There is improved thermodynamic efficiency of the hypertrophied myocardium when perfused at a physiological pressure, but when perfused at a reduced pressure, ventricular function, phosphorylation potential and pHi decline in rat hearts after three weeks of aortic constriction, indicating an impairment of coronary reserve.

Animals↗

PubMed1990

Calcium inhibition of glycolysis contributes to ischaemic injury.

STUDY OBJECTIVE: The purpose of the study was to confirm that [Ca2+]i and .[H+]i increase during ischaemia in hypertensive hearts but not in thyrotoxic hearts, and that the rise in [Ca2+]i and [H+]i inhibits glycolysis, causing a rise in phosphomonoester sugars and thereby influencing postischaemic recovery. DESIGN: Rats were made hypertensive by aortic banding and thyrotoxic by injection of L-thyroxine. [Ca2+]i was studied in isolated hearts by surface fluorometry assessing calcium dependent changes in the fluorescent dye INDO-1, while [pH]i and phosphomonoester sugars were studied by 31P nuclear magnetic resonance (NMR). Global ischaemia was carried out by turning off all flow to the heart for 30 min. Hearts were then reperfused for 30 min. SUBJECTS: 72 Sprague-Dawley rats, weight 500-600 g, were used. Left ventricular hypertrophy was generated by aortic banding in 36, half of which were treated with verapamil. Eighteen were injected with L-thyroxine and there were 18 controls. MEASUREMENTS AND RESULTS: With all groups, developed pressure immediately declined after the onset of global ischaemia. During ischaemia the phosphomonoester sugars rose less in the hearts of thyrotoxic rats and the verapamil treated aortic constricted rats than in those of untreated aortic constricted and normal rats. During ischaemia there was no significant difference in [pH]i among the four groups. During ischaemia intracellular calcium rose least in thyrotoxic and verapamil treated aortic constricted rats, and most in untreated aortic constricted and normal rats. Intracellular calcium rose 10-15 min after the onset of ischaemia in verapamil treated pressure overload and control hearts; calcium rose immediately after the onset of ischaemia in the untreated aortic constricted hearts, but negligibly in hearts from thyroxine treated animals. Verapamil treatment of the aortic constricted hearts prevented the rise in intracellular calcium, and attenuated phosphomonoester sugar accumulation. Postischaemic recovery was complete in hearts in thyroxine treated and verapamil treated aortic constricted rats, but not in hearts from untreated aortic constricted and normal rats. Postischaemic recovery was inversely related to ischaemic diastolic [Ca2+]i and phosphomonoester sugar levels, but was not related to ischaemic values for [pH]i. CONCLUSIONS: Postischaemic recovery may depend on the ability of the cell to maintain mitochondrial activity as evidenced by oxygen consumption, thereby controlling the voltage of the cell, and influencing the ability of the myocardium to maintain its calcium homeostasis.

Animals↗

PubMed1990

Postischemic recovery of mechanical performance and energy metabolism in the presence of left ventricular hypertrophy. A 31P-MRS study.

The present study was undertaken to define the effects of left ventricular hypertrophy on postischemic recovery of myocardial performance and high energy phosphate metabolism. Hemodynamics and 31P-magnetic resonance spectra were monitored simultaneously in the isolated Langendorff-perfused rat heart during 30 minutes of ischemia and 30 minutes of reperfusion. Left ventricular hypertrophy was produced by either suprarenal aortic constriction or chronic thyroxine administration. In chronic pressure overload hypertrophy, minimal coronary resistance was significantly higher (p less than 0.001) and the loss of purine nucleosides in the coronary effluent during early reperfusion significantly larger (p less than 0.001) compared with both normal hearts and thyroxine-induced hypertrophied hearts. Postischemic recovery of the baseline values for left ventricular developed pressure and phosphorylation potential was 43 +/- 4% and 82 +/- 4%, respectively, in chronic pressure overload hypertrophied hearts; 86 +/- 4% and 91 +/- 3%, respectively, in normal hearts (chronic pressure overload hypertrophy versus normal hearts, p less than 0.001 and p less than 0.05); and 100 +/- 4% and 98 +/- 2%, respectively, in thyroxine-induced hypertrophied hearts (normal hearts versus thyroxine-induced hypertrophied hearts, p less than 0.05 and p less than 0.05). Recovery after reperfusion was not related to intracellular pH, ATP, phosphocreatine, or inorganic phosphate levels during ischemia. Also, recovery was not related to developed pressure or oxygen consumption before ischemia. However, recovery was inversely related to coronary resistance and directly related to coronary flow before ischemia. Thus, functional and/or anatomic alterations of the coronary vascular bed and a greater loss of purine nucleosides during reperfusion are likely responsible for the attenuated compensatory response to ischemia and reperfusion in left ventricular hypertrophy induced by chronic pressure overload. On the other hand, the excess muscle mass per se does not seem to alter recovery, since thyroxine-induced myocardial hypertrophied hearts responded at least as well as normal hearts.

Animals↗

PubMed1990

Dobutamine potentiates amrinone's beneficial effects in moderate but not in advanced heart failure. 31P-MRS in isolated hamster hearts.

There is controversy as to whether potent inotropic agents are beneficial or detrimental in moderate to severe heart failure. Accordingly, we studied the effects of amrinone, amrinone plus dobutamine, and dobutamine alone on mechanical performance, myocardial oxygen consumption, and high energy phosphate metabolism in different stages of congestive heart failure in the cardiomyopathic Syrian hamster. In hearts with moderate heart failure, administration of amrinone, amrinone plus dobutamine, and dobutamine alone increased developed pressure significantly, whereas the phosphorylation potential increased significantly only with amrinone and amrinone plus dobutamine. In hearts with advanced heart failure, administration of amrinone and amrinone plus dobutamine increased developed pressure significantly, whereas dobutamine alone had no effect. The phosphorylation potential improved significantly only with amrinone. Thus, amrinone improved mechanical performance and mitochondrial activity in both heart failure states. Dobutamine potentiated amrinone's beneficial effects in moderate heart failure, but negated the positive inotropic effect of amrinone in advanced heart failure. Therefore, hearts responded differently to potent inotropic agents depending on the severity of heart failure.

Amrinone↗

PubMed1989

Reversibility of chronic alcohol cardiac depression: 31P magnetic resonance spectroscopy in hamsters.

In order to investigate the reversibility of chronic alcohol cardiac depression, hamsters were fed with 50% ethanol for 3 1/2 months, reaching serum alcohol levels of 0.13 +/- 0.11 g/dl (mean +/- SD). Alcohol was then withdrawn for 2 days. Isolated hearts were perfused according to a modified Langendorff method. Energy metabolites were studied using 31P magnetic resonance spectroscopy of isolated perfused hearts standardized by HPLC analysis of freeze-clamped tissue. Total intracellular calcium [Ca2+]i was measured with atomic absorption spectrophotometry, marking the extracellular space in vivo with K(CoEDTA). In alcohol-treated hamster hearts developed pressure was significantly depressed compared to controls. End-diastolic pressure was significantly increased. Coronary flow was not changed, whereas oxygen consumption and high-energy phosphate levels were significantly depressed. Intracellular pH was significantly decreased. [Ca2+]i was significantly increased. Heart weights were significantly lower. After alcohol withdrawal ventricular function, high-energy phosphate levels, and [Ca2+]i were not significantly different from control. The results indicate that chronic alcohol consumption depresses ventricular function and energy levels and also leads to myocardial acidosis. The increase in intracellular calcium likely causes mitochondrial dysfunction. Withdrawal of alcohol is associated with reversibility of functional and energetic cardiac depression.

Animals↗