Biomedical subjects

S T Wu

Publications and source records attributed to S T Wu.

At least 37 records · Page 2Linked to original sources

PubMed1994

Relationship between intracellular calcium and oxygen consumption: effects of perfusion pressure, extracellular calcium, dobutamine, and nifedipine.

All of the mechanisms that connect the cardiac mechanical work load with energy production have not been clearly defined. The purpose of this study was to evaluate the relationship between intracellular calcium and oxygen consumption in intact hearts, to further understand this relationship. Intracellular calcium was measured in isolated nonworking perfused rat hearts loaded with Indo-1 by means of a surface fluorometry technique. Glucose was used as a substrate. Myocardial contraction and oxygen consumption were modulated by perfusion pressure (80, 110, and 140 cm of water), extracellular calcium (1, 2, 3, and 4 mmol/L), dobutamine (10(-6) mol/L), and nifedipine (10(-6) mol/L). With all of these interventions there was a close correlation between intracellular calcium (systolic, diastolic, and amplitude) and oxygen consumption or left ventricular developed pressure. Observations in this study support the hypothesis that intracellular calcium plays a regulatory role in the link between cardiac mechanics and energy production.

Animals↗

PubMed1994

Intracellular calcium transients in potentiated contractions induced by multiple extrasystolic beats in isolated perfused rat hearts.

Mechanisms underlying contractile potentiation induced by multiple extrasystolic contractions (ESC) were evaluated with surface fluorometry in isolated perfused rat hearts loaded with Indo-1/AM. After baseline pacing with a 400 ms interval, 1-25 ESC were interposed with a regular 160 ms interval followed by the postextrasystolic beat with a 400 ms interval. With an increase in the ESC number, left ventricular developed pressure and peak positive dP/dt increased in an exponential manner, reaching a plateau, that was the same for 3 extracellular Ca2+ ([Ca2+]o; 0.55 (n = 9), 1.25 (n = 11) and 2.75 mM (n = 7). Increased [Ca2+]o shifted this relationship left and upward, and with 2.75 mM [Ca2+]o developed pressure and dP/dt decreased after the maximum potentiation was obtained. The relationship between the ESC number and the amplitude of the Indo-1 fluorescence (F400/F510; an index of intracellular Ca2+ ([Ca2+]i)) was also exponential and was shifted left and upward by high [Ca2+]o; however, it lacked the declining phase. Thus, the relationship between the amplitude of F400/F510 and developed pressure or dP/dt consisted of a positively linear part until the maximum potentiation was obtained and a negatively linear part with a further increase in the amplitude of F400/F510. This observation suggests that although contractile potentiation is mediated by increased [Ca2+]i transients, the maximum response might be determined by the responsiveness of the sarcomere.

Animals↗

PubMed1994

Nature of [Ca2+]i transients during ventricular fibrillation and quinidine treatment in perfused rat hearts.

We studied intracellular Ca2+ concentration ([Ca2+]i) and the electrocardiographic signals during pacing-induced ventricular fibrillation (VF) and quinidine treatment (0.4 mg/min) using surface fluorometry in indo 1-acetoxymethyl ester (AM)-loaded perfused rat hearts. [Ca2+]i was evaluated as the indo 1 fluorescence ratio (F400/F510) and expressed as a percentage of the control amplitude of F400/F510 transients. F400/F510 increased to approximately 250% during 2- (n = 14) or 20-min (n = 9) VF. Quinidine significantly decreased F400/F510 by 60% after 2-min VF; however, this effect was blunted after 20-min VF. After 2-min VF, F400/F510 and left ventricular pressure recovered almost to the control level. However, recovery of F400/F510 and ventricular function was poor after 20-min VF. The relationship between [Ca2+]i and the electrocardiogram (ECG) during VF was evaluated by power spectrum analysis of F400/F510 and ECG signals. During VF (25 +/- 3 Hz) with high irregularity, there were no clear [Ca2+]i transients (n = 110). When the cardiac rhythm (22 +/- 3 Hz) was regular, including ventricular tachycardia, there were recognizable [Ca2+]i signals with dominant frequencies that were the same (n = 2), one-half (n = 12), or one-third (n = 1) of the ECG frequencies. The highest frequency of the [Ca2+]i transients was 19 Hz. During quinidine treatment, the VF rate decreased significantly, and clear [Ca2+]i transients were noted in all records responding to every one or two ECG signals. The conclusions were the following: 1) [Ca2+]i responds to electrical signals rapidly (up to 19 Hz) during VF. This fast [Ca2+]i response is a probable cause of high [Ca2+]i during VF. 2) Quinidine decreased [Ca2+]i after 2-min VF possibly in part by slowing the VF and [Ca2+]i transients rates. 3) 20-min VF caused [Ca2+]i overload and poor functional recovery after defibrillation.

Animals↗

PubMed1993

Simple 24-hour preservation of rabbit hearts with hexanol and pyruvate cardioplegia.

The effectiveness of a newly developed crystalloid cardioplegic solution containing 4 mM 1-hexanol and 10 mM pyruvate was compared with St Thomas' Hospital solution. After control perfusion with a Langendorff method, rabbit hearts (n = 7 for each group) were arrested and stored in these solutions (4 degrees C) for 24 h and subsequently reperfused for 45 min. The hexanol solution preserved both left ventricular systolic and diastolic function significantly better than St Thomas' Hospital solution. Developed pressure was significantly higher after preservation with the hexanol solution than with the St Thomas' Hospital solution at left ventricular balloon volumes larger than the mid volume (P < 0.05). The maximum developed pressure values after storage with the hexanol and St Thomas' Hospital solution were 77% and 42% of the maximum control values, respectively. Values for end-diastolic pressure at the maximum ventricular volume were 26.1 +/- 9.8 and 66.7 +/- 24.6 mmHg for the hexanol and St Thomas' Hospital solution, respectively (P < 0.05). Creatine kinase release during the first 15 min of reperfusion was significantly lower with the hexanol solution as compared to St Thomas's Hospital solution (28.3 +/- 8.3 vs 92.9 +/- 52.6 IU/g wet weight, P < 0.05). In conclusion, a hexanol cardioplegic solution may be suitable for long-term cardiac preservation. Further evaluation of the effectiveness and safety of this solution is warranted.

Animals↗

PubMed1993

Eighteen-hour preservation of rat hearts with hexanol and pyruvate cardioplegia.

OBJECTIVES: The aim of this study was to evaluate the effectiveness of 1-hexanol as an arresting agent and pyruvate as a substrate in a cardioplegic solution. BACKGROUND: Heart transplantation is limited in part by the short preservation time of donor hearts. Better preservation techniques would improve patient survival and the time and geographic area for using donor hearts. We previously showed that a cardioplegic solution containing ethanol and pyruvate was superior to a conventional high potassium cardioplegic solution in 24-h cold storage of hamster hearts. Hexanol, a more potent arresting agent than ethanol, might be a more suitable alcohol. METHODS: Rat hearts were arrested and stored for 18 h at 4 degrees C with an ethanol (3 vol% = 510 mmol/liter) or 1-hexanol (4 mmol/liter) and pyruvate (10 mmol/liter) cardioplegic solution, St. Thomas' Hospital solution and Stanford solution and subsequently reperfused for 1 h at 35 degrees C. In other groups of hearts, basal oxygen consumption and rest intracellular calcium (Indo 1 technique) were evaluated during ethanol-, hexanol- and potassium-induced cardiac arrest. RESULTS: The percent recovery of left ventricular developed pressure and rate-pressure product were significantly better with the hexanol cardioplegic solution (67 +/- 21% and 58 +/- 19%, respectively; p < 0.05 for all comparisons) compared with the ethanol (10 +/- 7% and 5 +/- 4%), St. Thomas' Hospital (14 +/- 6% and 10 +/- 5%) and Stanford solutions (2 +/- 2% and 2 +/- 1%, respectively). Exclusion of ethanol and hexanol from storage solutions did not influence functional recovery. Values for oxygen consumption after 15- and 30-min ethanol- and hexanol-induced arrest were significantly lower than those after potassium-induced cardiac arrest. There was no difference in the rest intracellular calcium during cardiac arrest induced by the three arresting agents. CONCLUSIONS: A hexanol and pyruvate cardioplegic solution was more favorable than ethanol or conventional solutions for long-term cold storage of rat hearts. The beneficial effects of hexanol may have been provided in part by lower energy consumption during hexanol-induced cardiac arrest. These results may have implications for preservation of hearts for heart transplantation.

Animals↗

PubMed1993

Acute effects of ethanol on cardiac function and intracellular calcium in perfused rat heart.

OBJECTIVE: The aim was to evaluate effects of ethanol on cardiac function and intracellular Ca2+ ([Ca2+]i) in perfused rat hearts. METHODS: A Langendorff perfused rat heart preparation was used. Changes in [Ca2+]i were evaluated by surface fluorometry in hearts loaded with Indo 1-AM. RESULTS: Clinically relevant concentrations of ethanol (0.2 or 0.4% vol/vol) had no significant haemodynamic effects. High concentrations of ethanol (1, 2, 3, and 4% vol/vol) showed dose dependent decreases in developed pressure and the systolic peak and overall amplitude of the Indo 1 fluorescence transients (identical to [Ca2+]i), that were partially antagonised by high extracellular Ca2+ ([Ca2+]o = 4 mM). The ethanol concentrations that decreased developed pressure by 50% were 1.4 and 2.6% in the low (1.5 mM) and high [Ca2+]o, respectively. Four per cent ethanol decreased the amplitude of Indo 1 fluorescence transients to 54.5(SD 3.1) and 64.6(7.9)% of control values in the low and high [Ca2+]o, respectively. A relationship between the amplitude of Indo 1 fluorescence and developed pressure was fitted to a single sigmoid curve irrespective of [Ca2+]o. During ethanol washout, there was a dose dependent overshoot of the fluorescence ratio. CONCLUSIONS: Only high concentrations of ethanol depressed left ventricular function in a dose dependent manner by decreasing the amplitude of [Ca2+]i transients. High [Ca2+]o partially antagonised acute alcoholic cardiac depression by increasing the amplitude of [Ca2+]i transients. [Ca2+]i is a mediator of the acute cardiac effects of ethanol in perfused intact rat hearts.

Animals↗

PubMed1993

Effects of perfusion pressure on intracellular calcium, energetics, and function in perfused rat hearts.

Effects of perfusion pressure in a range from 50 to 140 cmH2O on intracellular Ca2+ concentration ([Ca2+]i) were evaluated along with cardiac function, energy metabolism, and left ventricular geometry in a concentration of 2 or 4 mM of extracellular Ca2+ ([Ca2+]o) in isovolumic perfused rat hearts. [Ca2+]i was evaluated with a surface fluorometry technique in hearts loaded with indo-1/AM. The systolic and diastolic values and the amplitude (difference between systolic and diastolic values) of indo-1 fluorescence ratio (an index of [Ca2+]i) were linearly related to perfusion pressure. Changes in the fluorescence ratio were harmonious with rapid changes in left ventricular pressure and stabilized within 30-40 s after changes in perfusion pressure. Developed pressure and O2 consumption were closely, linearly correlated with the fluorescence ratio irrespective of [Ca2+]o. Left ventricular end-diastolic wall thickness, measured by 2-dimensional echocardiography, paralleled perfusion pressure and showed a good correlation with the fluorescence ratio. Diastolic myocardial adenosine 3',5'-cyclic monophosphate significantly decreased only at the lowest perfusion pressure. The ln[phosphocreatine]/[Pi] also changed with altered perfusion pressure. In conclusion, perfusion pressure modulates [Ca2+]i, which in turn regulates myocardial contraction and associated O2 utilization.

Animals↗

PubMed1992

In vitro release of nitroglycerin from topical products by use of artificial membranes.

An in vitro testing method for measuring the release of nitroglycerin from topical drug products was evaluated. The method involved measuring the amount of nitroglycerin that diffused from ointments and patches through various synthetic membranes into receptor fluid contained in a modified Franz diffusion cell. Plots of the amount of nitroglycerin released against the square root of time for all 10 synthetic membranes were linear. Five membranes (group I) were found to release nitroglycerin at similar rates (difference not significant; p > 0.05). Use of the other five membranes (group II) in diffusion cells resulted in release rates significantly slower than those of group I membranes (p < 0.05). Rapid permeation of nitroglycerin from a solution through a polysulfone membrane demonstrated a lack of significant diffusion barrier properties of this membrane. Rates of release of nitroglycerin from commercially available ointments were found to be similar. A comparison of three commercial nitroglycerin patches revealed that these products released nitroglycerin at different rates in vitro.

Administration, Cutaneous↗

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↗

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↗

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

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↗