[Effect of metformin combined with intermittent fasting on endoplasmic reticulum stress after cerebral ischemia-reperfusion in mice].

Objective: To explore the effect of metformin combined with intermittent fasting on endoplasmic reticulum stress after cerebral ischemia-reperfusion injury in mice. Methods: One hundred 10-Week-old healthy KM mice of SPF grade, weighing 25-28 g, were divided into 5 groups by the random number table method: sham group, focal cerebral ischemia group (I/R group), intermittent fasting group (IF group), metformin group (Met group), metformin+intermittent fasting group (Met+IF group). In IF group, food was provided ad libitum from 8∶00 to 16∶00 daily, but the mice were fasted for the rest of the time. In Met group, the mice underwent intraperitoneal injection of metformin (10 mg/kg). In Met+IF group, the mice received the same eating method as the IF group and the same method of metformin injection as Met Group. In Sham group, I/R group and IF group, the mice were intraperitoneally injected with equal volume of normal saline. Mice in all groups were not restricted to drinking water. Random plasma glucose and body weight changes in mice during preconditioning were monitored, and a focal cerebral ischemia-reperfusion model was established 14 days later. The cerebral infarction volume was measured after 1 hour of ischemia and 24 hours of reperfusion. The brain tissues of mice were subjected to Western blot to detect the contents of endoplasmic reticulum stress-related proteins, including glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and apoptosis proteins (Caspase-3 and Cleaved-caspase 3). Results: After different interventions, there was no significant difference in random plasma glucose changes among the four groups (all P<0.05). The blood glucose level of the mice in the Met+IF group was lower than the sham group, I/R group, IF group and Met group (all P<0.05). GRP78/ß-actin in sham group, I/R group, IF group, Met group, IF+Met group were 0.48±0.05, 1.35±0.10, 0.94±0.05, 0.70±0.14, 0.41±0.37, respectively; CHOP/ß-actin were 0.27±0.04, 1.03±0.03, 0.72±0.04, 0.63±0.04, 0.44±0.01, respectively; Caspase-3/ß-actin were 0.51±0.04, 1.04±0.04, 0.83±0.03, 0.76±0.03, 0.63±0.05, respectively; Cleaved-Caspase-3/ß-actin were 0.17±0.06, 1.01±0.20, 0.75±0.06, 0.51±0.12, 0.29±0.08, respectively, with statistically significant differences (all P<0.001). The counts of GRP78-positive cells in the hippocampus immunohistochemistry in the sham group, I/R group, IF group, Met group, and IF+Met group were 53±5, 192±11, 162±12, 140±10, 114±13, respectively, while the counts of CHOP-positive cells were 35±4, 177±12, 120±12, 100±7, 69±10, respectively, with statistically significant differences (all P<0.001). The relative volume of cerebral infarction in I/R group, IF group, Met group and IF+Met group were 0, 0.333±0.046, 0.258±0.023, 0.116±0.039, 0.111±0.039, respectively, and there were statistically significant differences (all P<0.001). Conclusion: Both Metformin and intermittent fasting can alleviate endoplasmic reticulum stress after cerebral ischemia and reperfusion in mice, and the combination of the two has a better effect.

[Application of ROC and PR curves in the evaluation of clinical diagnostic testing].

This study reviewed the concepts and properties of the receiver operating characteristic (ROC) curve and precision recall (PR) curve, and made suggestions on the application of two curves based on the prevalence in combination with the results of simulation data. This study demonstrated that the ROC curve and PR curve had different properties, which could reflect the performance of diagnostic methods from various aspects. These two curves should be selected with a consideration of prevalence and clinical scenarios. When the prevalence was less than 20%, especially less than 5%, the PR curve could be adopted.

Synchronous renal cell carcinoma and pheochromocytoma presenting as acute decompensated heart failure.

We report a 49-year-old woman who presented with a hypertensive crisis and acute heart failure and reduced left ventricular systolic function. An abdominal ultrasonography revealed a huge lobulated heterogeneous mass at the lower pole of the right kidney and a mass over the left suprarenal area, which were further delineated by magnetic resonance imaging. The patient underwent laparoscopic right radical nephrectomy and left adrenalectomy. Histopathological analysis confirmed the diagnoses of clear cell renal cell carcinoma of the right kidney with metastasis to the lung; and atypical pheochromocytoma of the left adrenal gland. Target therapy was initiated, which resulted in stabilization of the patient's tumors and the recovery of her heart function. To avoid a delayed diagnosis and catastrophic outcome, clinicians should consider such rare causes of acute decompensated heart failure.

miR-1 association with cell proliferation inhibition and apoptosis in vestibular schwannoma by targeting VEGFA.

A growing body of research has demonstrated the tumor suppressive function of microRNA (miR)-1 in many cancers. Our study aimed to investigate its role in vestibular schwannoma (VS). We examined miR-1 expression in 95 VS specimens and 79 normal vestibular nerves using quantitative real-time polymerase chain reaction. Moreover, miR-1 mimics, miR-1 inhibitors, and negative control oligonucleotides were transfected into HEI-193 human VS cells to investigate the functional significance of miR-1 expression in this condition at a cellular level. Finally, the role of vascular endothelial growth factor A (VEGFA) in miR-1-mediated HEI-193 cell growth was confirmed. miR-1 levels were significantly reduced in VS specimens compared with normal vestibular nerve tissues (P < 0.001). In addition, low levels of miR-1 were associated with larger tumor volumes. In functional assays, miR-1 suppressed HEI-193 cell proliferation and colony formation, and enhanced apoptosis. VEGFA was verified as a target gene of miR-1, and VEGFA overexpression partially negated the effects of miR-1 on HEI-193 cells. These findings suggest that miR-1 suppresses VS growth by targeting VEGFA, and should be considered as a potential therapeutic target for treatment of this condition.

Exploration of the association between chronic periodontal disease and erectile dysfunction from a population-based view point.

Several cross-sectional studies have indicated an association between chronic periodontal disease (CPD) and cardiovascular disease and metabolic syndrome. Erectile dysfunction (ED) also shares pathological mechanisms with these diseases. Using a nationwide population-based data set, we examined the association between ED and CPD and assessed the effect of dental extraction (DE) on ED prevalence in different aged CPD populations in Taiwan. We identified 5105 patients with ED and randomly selected 10 210 patients as controls. Of these patients, 2617 (17.09%) were diagnosed with CPD according to the index data: 1196 (23.43%) in the ED group and 1421 (13.92%) in the control group. After adjusting for comorbid factors, patients with ED were more likely to have been diagnosed with prior CPD than controls (OR = 1.79, 95% CI = 1.64-1.96, P < 0.001). Moreover, the association was much stronger in the populations aged less than 30 years (OR = 2.13, 95% CI = 1.23-3.70, P < 0.001) and more than 59 years (OR = 2.27, 95% CI = 1.99-2.59, P < 0.001). Dental extraction seems to attenuate damage to the penile endothelial beds caused by CPD-related inflammation and overcame the process of ED in the middle-aged and older populations.

The safety and effectiveness of TM81, a Chinese herbal medicine, in the treatment of type 2 diabetes: a randomized double-blind placebo-controlled trial.

AIM: TM81 (or Tang-Min-Ling-Wan) is a Chinese medicine. Previous studies suggested that this medicine is effective for treating type 2 diabetes. This controlled trial evaluated the safety and effectiveness of TM81 in the treatment of type 2 diabetic patients. METHODS: This study was a large-scale controlled clinical trial to evaluate the safety and effectiveness of TM81 on type 2 diabetes. After a 2-week run-in period, 480 overweight type 2 early-stage diabetic patients [35-65 years old, HbA1c ≥ 7.0%, fasting plasma glucose (FPG) 7.0-13.9 mM or 2 h plasma glucose (PG) > 11.1 mM, body mass index (BMI) ≥ 24 kg/m(2)] were enrolled. These patients were divided into a TM81 group and placebo group in a 3 : 1 ratio. The subjects received 6 g TM81 or placebo, three times daily for 12 weeks. RESULTS: After treatment, the HbA1c decrease was 1.02% in the TM81 group versus 0.47% in the placebo group. The FPG decreased 0.8 ± 0.1 mM in the TM81 group versus an increase of 0.2 ± 0.2 mM in the placebo group. The PG decreased 2.7 ± 0.3 mM in the TM81 group versus a decrease of 0.9 ± 0.4 mM in the placebo group (all p < 0.05). The TM81 was more effective for patients with higher baseline HbA1c levels. The TM81 group also showed improved ß-cell function and increased homeostatic model assessment (HOMA)-ß. In addition, body weight, BMI and waist circumference of subjects in the TM81 group were reduced, and the symptoms related to diabetes were improved. There were no significant differences in the types and frequency of adverse reactions between the two groups. CONCLUSIONS: The data showed that TM81 is effective in controlling blood glucose level and is safe to use in patients with early-stage type 2 diabetes.

Prolonged hyperkalemia following unilateral adrenalectomy for primary hyperaldosteronism.

Hypokalemia associated with aldosterone-producing adenomas (APA) are almost corrected following successful unilateral adrenalectomy. Prolonged hyperkalemia after unilateral adrenalectomy is rarely reported and may be overlooked. We describe a 62-year-old man who presented with fatigue and dizziness 2 weeks after unilateral adrenalectomy for aldosterone-producing adenomas. Physical examination showed decreased skin turgor and postural hypotension. Laboratory studies revealed hyperkalemia (6.3 mmol/l) with a low transtubular potassium gradient of 5. A relatively low plasma aldosterone concentration and high plasma renin activity in the setting of normal plasma cortisol and adrenocorticotropic hormone levels lead to a diagnosis of functional hypoaldosteronism. Fludrocortisone 0.2 mg/day for one week completely corrected his hyperkalemia which recurred after cessation of fludrocortisone. Long-term suppression of contralateral aldosterone synthesis by APA and/or chronic untreated hypokalemia may have accounted for the development of prolonged hyperkalemia after unilateral adrenalectomy. Serum potassium concentration following unilateral adrenalectomy must be meticulously monitored to avoid life-threatening hyperkalemia.

Acute fulminant colon cancer metastasis after renal transplantation.

We report a 52-year-old male with no family history of colonic cancer, who was found to have advanced colonic cancer with metastases two months post renal transplantation. With this case, we highlight the possibility of acute fulminant cancer metastases within short period after renal transplantation and the importance of periodic colorectal cancer screening pre-transplant. To our knowledge, this case is not yet reported in the literature, especially with such presentation of acute fulminant colonic cancer metastases post renal transplantation.

Waldenström macroglobulinaemia presenting as a perirenal mass: a case report.

Perirenal masses are a rare manifestation of Waldenström macroglobulinaemia (WM). We report a 70-year-old male diagnosed with Waldenström macroglobulinaemia arising as a huge perirenal mass, which was discovered by abdominal ultrasound and computed tomography. The patient underwent ultrasound-guided aspiration biopsy and the histopathological examination showed a monoclonal lymphoplasmocitoid proliferation of B-cells arranged in a diffuse pattern. This case report shows not only the importance of image and biopsy studies, but also the good response to chemotherapy with the CHOP regimen.

Holmium: yttrium-aluminum-garnet laser endoureterotomy for benign ureteral strictures: a single-centre experience.

PURPOSE: This study aimed to report the results of endoureterotomy for benign ureteral strictures using the holmium: yttrium-aluminum-garnet laser. MATERIAL AND METHODS: Nineteen patients (8 men and 11 women, mean age 51.47 years) underwent holmium: yttrium-aluminum-garnet laser endoureterotomy for benign ureteral strictures (8 proximal, 3 middle, and 8 distal) using semi-rigid ureteroscopy and 360-microm fibre at 1.2 J/pulse and 10 Hz. After completion of the incision, a 7-Fr double-J ureteral stent was left for 6 weeks. Thereafter, the patients were followed-up by ultrasound and/or intravenous urography at 3-6 monthly intervals. RESULTS: Success was defined as the absence of symptoms plus radiographic resolution of obstructions as assessed by diuretic renography and/or intravenous urography. With a mean follow-up of 40.2 months, success was achieved in 10 (52.6%) of the 19 patients. Nine patients developed recurrent strictures and were considered treatment failures. The stricture length and severity of hydronephrosis correlated with successful outcome, but gender, aetiology, side and location of strictures did not predict outcome. CONCLUSIONS: Although endoureterotomy using a holmium : yttrium-aluminum-garnet laser has an equivocal outcome, the procedure is recommended as a safe, less invasive therapeutic option for the initial management of benign ureteral strictures.

Association between lower urinary tract symptoms and sexual dysfunction in Taiwanese men.

The study investigated the association between lower urinary tract symptoms (LUTS) and sexual dysfunction in ageing men. It was a cross-sectional study in an unselected consecutive sample of 398 men aged >40 years attending a urology clinic. LUTS and sexual function were assessed by validated symptom scales, including the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function-5 (IIEF-5). Clinically the severity of total and obstructive IPSS showed no significant correlation with age, but irritative IPSS is statistically correlated with age (P < 0.05). The prevalence of moderate to severe ED (IIEF-5 < 12) was significantly associated with LUTS severity (P < 0.05) and the severity of IIEF-5 correlated significantly with age (P < 0.01). A consistent inverse correlation was found between IIEF-5 and IPSS severity across the age groups, with the strongest effect within aged 60 to 69 years (r = -0.286, P < 0.01). The irritative IPSS showed a significant correlation with IIEF-5 severity across all age groups. These results reveal a significant correlation between LUTS and the severity of ED, especially on the irritative domain.

Follow-up of bilateral subthalamic deep brain stimulation for Parkinson's disease.

PURPOSE: To demonstrate the effects of bilateral subthalamic deep brain stimulation (STN-DBS) in the treatment of Parkinson's disease (PD) after 4-45 months' follow-up. METHOD: Between 04/01 and 12/04, 46 PD patients were operated on with bilateral STN-DBS. All of them were evaluated with Unified Parkinson's Disease Rating Scale (UPDRS) parts II-V before surgery and 4-45 months after surgery. The amelioration of miscellaneous symptoms and decrease of medication dose, respectively, were compared. Main side effects were observed. FINDINGS: After surgery, both the score of activities of daily living (ADL) and the UPDRS motor score decreased significantly (p < 0.001). Among the PD symptoms, tremor was improved best. Rigidity, bradykinesia, axial symptoms, facial expression and dyskinesia were all improved, although to a lesser extent, while speech was not improved. Medication dose was decreased significantly (p < 0.001). According to the time of follow-up, 4 groups were classified (4-12 months, 13-24 months. 25-36 months and 37-45 months group). ADL, UPDRS motor score and dyskinesia subscore improvement were compared among these groups. No significant difference existed. No life threatening complications occurred. Main side effects included hypophonia, dyskinesia, confusion, depression. CONCLUSIONS: Bilateral STN-DBS is a satisfying surgical method for the treatment of advanced PD. It can improve the cardinal PD symptoms up to 45 months. Complications and side effects were rare and usually temporary or reversible.

Data-driven magnetohydrodynamic modelling of a flux-emerging active region leading to solar eruption.

Solar eruptions are well-recognized as major drivers of space weather but what causes them remains an open question. Here we show how an eruption is initiated in a non-potential magnetic flux-emerging region using magnetohydrodynamic modelling driven directly by solar magnetograms. Our model simulates the coronal magnetic field following a long-duration quasi-static evolution to its fast eruption. The field morphology resembles a set of extreme ultraviolet images for the whole process. Study of the magnetic field suggests that in this event, the key transition from the pre-eruptive to eruptive state is due to the establishment of a positive feedback between the upward expansion of internal stressed magnetic arcades of new emergence and an external magnetic reconnection which triggers the eruption. Such a nearly realistic simulation of a solar eruption from origin to onset can provide important insight into its cause, and also has the potential for improving space weather modelling.

A novel association of neuropilin-1 and MUC1 in pancreatic ductal adenocarcinoma: role in induction of VEGF signaling and angiogenesis.

We report that Mucin1 (MUC1), a transmembrane glycoprotein that is overexpressed in >80% of pancreatic ductal adenocarcinoma (PDA), induced a pro-angiogenic tumor microenvironment by increasing the levels of neuropilin-1 (NRP1, a co-receptor of vascular endothelial growth factor (VEGF)) and its ligand VEGF. Expression of tumor-associated MUC1 (tMUC1) positively correlated with NRP1 levels in human and mouse PDA. Further, tMUC1hi PDA cells secreted high levels of VEGF and expressed high levels of VEGF receptor 2 (VEGFR2) and its phosphorylated forms as compared with tMUC1low/null PDA. This enabled the tMUC1hi/NRP1hi PDA cells to (a) induce endothelial cell tube formation, (b) generate long ectopic blood vessels and (c) enhance distant metastasis in a zebrafish xenograft model. Concurrently, the proteins associated with epithelial-to-mesenchymal transition, N-cadherin and Vimentin, were highly induced in these tMUC1/NRP1hi PDA cells. Hence, blocking signaling via the NRP1-VEGF axis significantly reduced tube formation, new vessel generation and metastasis induced by tMUC1hi PDA cells. Finally, we show that blocking the interaction between VEGF165 and NRP1 with a NRP1 antagonist significantly reduced VEGFR signaling and PDA tumor growth in vivo. Taken together, our data suggest a novel molecular mechanism by which tMUC1 may modulate NRP1-dependent VEGFR signaling in PDA cells.

Salient effects of L-carnitine on adenine-nucleotide loss and coenzyme A acylation in the diabetic heart perfused with excess palmitic acid. A phosphorus-31 NMR and chemical extract study.

The beneficial effects of L-carnitine perfusion on energy metabolism and coenzyme A acylation were studied in isolated hearts from control and diabetic rats. All hearts were perfused at a constant flow rate with a glucose/albumin buffer which contained 2.0 mM palmitate. 31P-NMR was utilized to assess sequential phosphocreatine and ATP metabolism during 1 h of recirculation perfusion. L-Carnitine (5.0 mM final concentration) was added after 12 min of baseline recirculation perfusion. Frozen samples were taken after 1 h of recirculation perfusion for spectrophotometric analysis of high-energy phosphates and the free and acylated fractions of coenzyme A. L-Carnitine perfusion of diabetic hearts attenuated or prevented the reduction of ATP observed in untreated diabetic hearts. It also attenuated the accumulation of long-chain fatty-acyl coenzyme A. Although L-carnitine improved myocardial function in diabetic hearts, this was independent of any direct effect on physiological indices. Thus, the salutory effect of acute perfusion with L-carnitine on energy metabolism in the isolated perfused diabetic rat heart appears to be a direct effect on lipid metabolism.

Lipid-mediated impairment of normal energy metabolism in the isolated perfused diabetic rat heart studied by phosphorus-31 NMR and chemical extraction.

The relationship between extracellular palmitate and the accumulation of long-chain fatty-acyl coenzyme A with that of high-energy phosphate metabolism was investigated in the isolated perfused diabetic rat heart. Hearts were perfused with a glucose/albumin buffer supplemented with 0, 0.5, 1.2 or 2.0 mM palmitate. 31P-NMR was used to analyze phosphocreatine and ATP metabolism during 1 h of constant-flow recirculation perfusion. At the end of perfusion, frozen samples were taken for chemical analysis of high-energy phosphates and the free and acylated fractions of coenzyme A and carnitine. Perfusion of diabetic hearts with palmitate, unlike control hearts, caused a time-dependent and concentration-dependent reduction in ATP, despite normal and constant phosphocreatine. Concentrations of acid-soluble coenzyme A, long-chain-acyl coenzyme A and total tissue coenzyme A were elevated in palmitate-perfused diabetic hearts, while the total tissue carnitine pool was decreased. Increases in long-chain-acyl coenzyme A correlated with the reduction in myocardial ATP. This reduction in ATP could not be adequately explained by alterations in heart rate, perfusion pressure or vascular resistance.

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.

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.

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.