Perspective of healthcare providers on assessing the quality and accessibility of health services for chronic diseases in Jordan during Covid-19: a mixed method study.

BACKGROUND: Hospital services in all parts of the world were severely affected by the crisis caused by the Coronavirus pandemic. This was particularly concerning for patients who suffer from chronic diseases. AIM: This study aimed to: assess the level of quality and accessibility of chronic disease services from the perspectives of healthcare providers, assess the association between healthcare providers' socio-demographic factors and their perspectives on accessibility and quality level, and explore the providers' perspectives on the barriers and facilitators of quality and accessibility to chronic disease health services during the COVID -19 pandemic. METHOD: Design: An explanatory mixed method design was employed in this study using a questionnaire and focus group discussion approach. The questionnaire consisted of three sections including, demographic, accessibility, and quality. SAMPLE: A convenience sampling approach was used to collect the quantitative from 412 healthcare providers working at public, private, and teaching hospitals. A purposive sample of 12 healthcare providers were interviewed to collect the qualitative data. ANALYSIS: The quantitative data were analyzed using SPSS Statistics Version 25. The qualitative data was analyzed using the thematic analysis approach. RESULTS: This study found that the quality and accessibility of chronic disease services in northern Jordan were affected during COVID-19. Quantitative: The majority of the participants reported moderate level of accessibility and quality. Qualitative: Four main and six subthemes were identified: 1) Accessibility barriers including transportation and fear of infection; 2) Accessibility facilitators including availability of Personal Protective Equipment (PPE) and Covid-19 vaccination; 3) Quality barriers including staff shortage; 4) Quality facilitators including safety protocol. CONCLUSION: The quality and accessibility of chronic disease services were affected due to the healthcare system restating to address the Covid-19 pandemic. Different barriers and facilitators for chronic disease healthcare services accessibility and quality were identified. The findings of this study lay the ground for healthcare decision and policymakers to develop strategies and formulate polices to ensure these patients receive the needed healthcare services, and hence improve their health outcomes.

Abnormal cardiac function in the streptozotocin-diabetic rat. Changes in active and passive properties of the left ventricle.

To provide an integrated assessment of changes in systolic and diastolic function in diabetic rats, we measured conscious hemodynamics and performed ex vivo analysis of left ventricular passive-elastic properties. Rats given streptozotocin (STZ) 65 mg/kg i.v. (n = 14) were compared with untreated age-matched controls (n = 15) and rats treated with insulin after administration of STZ (n = 11). After 7 d, diabetic rats exhibited decreases in heart rate and peak developed left ventricular (LV) pressure during aortic occlusion. After 26 d of diabetes there were significant decreases in resting LV systolic pressure, developed pressure, and maximal +dP/dt, whereas LV end-diastolic pressure increased and the time constant of LV relaxation was prolonged. The passive LV pressure-volume relationship was progressively shifted away from the pressure axis, and the overall chamber stiffness constant was decreased. However, "operating chamber stiffness" calculated at end-diastolic pressure was increased at 7 d, and unchanged at 26 d. LV cavity/wall volume and end-diastolic volume were increased after 26 d of diabetes. Myocardial stiffness was unchanged at both time intervals. All of the above abnormalities were reversed by the administration of insulin. We conclude that the hemodynamic and passive-elastic changes that occur in diabetic rats represent an early dilated cardiomyopathy which is reversible with insulin.

Survival after myocardial infarction in rats: captopril versus losartan.

OBJECTIVES: This study sought to compare the effects of angiotensin-converting enzyme inhibition versus angiotensin II receptor blockade on survival in rats with myocardial infarction. BACKGROUND: The effects of specific nonpeptide angiotensin receptor blocking agents on survival after myocardial infarction are unknown. METHODS: Rats with a moderate to large myocardial infarction were treated with captopril (2 g/liter drinking water, n = 87) or losartan (2 g/liter drinking water, n = 96). Therapy was initiated immediately after coronary artery ligation and continued for 1 year. RESULTS: Uncensored median survival in captopril-treated rats that survived at least 48 h was 201.5 days versus 236.0 days for losartan-treated rats (p = 0.066). Median survival censored for rats with lung infections was 201.5 days in captopril-treated rats versus 243.0 days for losartan-treated rats (p = 0.028). Conscious hemodynamic measurements and remodeling data obtained at 1 year in the surviving rats (n = 5 for captopril; n = 9 for losarton) revealed no differences in heart weight, left ventricular pressure, dP/dt, cardiac index, time constant of relaxation or any variable of left ventricular remodeling. The only differences (mean +/- SD) were an increase in heart rate (293 +/- 19 vs. 266 +/- 15 beats/min, p < 0.05) and a decrease in peak developed pressure (153 +/- 21 vs. 180 +/- 16 mm Hg, p < 0.05) in the losartan-treated rats. CONCLUSIONS: We conclude that in this experimental model of heart failure, there was no significant difference between survival after angiotensin II receptor blockade with losartan and with angiotensin-converting enzyme inhibition with captopril.

Alterations in left ventricular relaxation during atrioventricular pacing in humans.

To determine whether the asynchronous left ventricular contraction-relaxation sequence that exists during right ventricular pacing alters left ventricular relaxation, measurements of both the maximal rate of decline of left ventricular pressure (peak negative dP/dt) and the time constant of left ventricular relaxation were obtained during atrial and atrioventricular (AV) pacing in 25 patients referred for diagnostic cardiac catheterization. Heart rate was maintained at 10 to 15 beats/min above the sinus rate at rest, and relaxation was assessed during atrial pacing, AV pacing and repeat atrial pacing. The patients were classified into two groups. Group 1 included 10 patients with normal left ventricular systolic function at rest (ejection fraction greater than 0.55) and without evidence of prior myocardial infarction. Group 2 included 15 patients with a depressed left ventricular ejection fraction or akinesia of one or more left ventricular segments on the contrast ventriculogram, or both. Heart rate, peak left ventricular systolic pressure, end-systolic pressure and end-diastolic pressure remained constant during atrial, AV pacing and repeat atrial pacing in all patients. In group 1 patients, the decrease in peak negative dP/dt (1,507 +/- 200 versus 1,424 +/- 187 mm Hg/s) and the increase in the time constant of left ventricular relaxation (48 +/- 11 versus 51 +/- 11 ms) during AV pacing was not significantly different when compared with values during atrial pacing.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of endothelial and inducible nitric oxide synthases inhibition on circulatory function in rats after myocardial infarction.

OBJECTIVES: To examine the relative roles of eNOS and iNOS (endothelial and inducible nitric oxide synthases) on basal and beta-adrenergic receptor (beta-AR)-stimulated arterial hemodynamic responses after myocardial infarction (MI). METHODS: Left ventricular (LV) pressures and steady-state and pulsatile arterial hemodynamics were measured at baseline, and after acute NOS inhibition with either NG-nitro-L-arginine methyl ester (L-NAME, 100 mg/kg) or iNOS inhibition with aminoguanidine (AG, 75 mg/kg) in sham-operated and MI Sprague-Dawley rats. RESULTS: In sham rats, L-NAME decreased (P < 0.05) peak positive LV dP/dt and aortic blood velocity by 19% and 53%, respectively, and increased (P < 0.05) mean arterial pressure (MAP); systemic vascular resistance, and LV end-diastolic pressure (EDP) by 20, 189 and 89%, respectively. The frequency-dependent components of hemodynamics including aortic input impedance modulus, characteristic impedance, and phase shift were increased (P < 0.05) with L-NAME, while pulsatile power was decreased (P < 0.05). AG increased (P < 0.05) aortic input impedance modulus and characteristic impedance but had no effect on any other hemodynamic variable. In MI rats, L-NAME decreased (P < 0.05) LV dP/dt and aortic blood velocity by 22 and 55%, respectively, and increased (P < 0.05) SVR by 108%. There was no effect of L-NAME on MAP or LV EDP in MI rats. After MI, AG increased (P < 0.05) heart rate and LV dP/dt but had no effect on other LV or pulsatile hemodynamic variables. Compared to sham rats, heart rate, LV dP/dt, and blood velocity-isoproterenol dose responses were shifted downward (P < 0.05), while SVR-isoproterenol dose response was shifted upward (P < 0.05) in MI rats. In sham rats, L-NAME potentiated (P < 0.05, at > 10(-2) micrograms/kg) the isoproterenol-induced increase in LV dP/dt and aortic blood velocity, and potentiated (P < 0.05) the isoproterenol-induced decline in SVR. As expected, AG had no effects on isoproterenol-stimulated hemodynamics in sham rats. After MI, there was no effect of L-NAME or AG on isoproterenol-stimulated hemodynamics. CONCLUSIONS: (1) Circulatory and cardiac responses to inhibition of NO by L-NAME suggest that eNOS, but not iNOS, is the principal regulator of integrated arterial hemodynamic function in rats. (2) Both basal and beta-AR-stimulated NO regulation of hemodynamic are attenuated after MI. (3) The attenuation of arterial hemodynamic effects after isoproterenol is mediated, in part, by alterations in the beta-AR-activation of eNOS system after MI.

Large artery remodeling during aging: biaxial passive and active stiffness.

To examine arterial mechanical changes during aging, pressure-radius and axial force-radius curves were measured in vivo in carotid arteries from 6- and 23-month-old Brown Norway X Fischer 344 rats. Incremental passive circumferential stiffness (measured at 50, 100, and 200 mm Hg) was higher (P<0.01) in the 23- compared with the 6-month-old rats (14.02+/-1.23 versus 6.58+/-1.51; 2.68+/-0.56 versus 0.99+/-0.34; 1.10+/-0.24 versus 0.69+/-0.15 dyne/mm2x10(3), respectively). Incremental passive axial stiffness was increased (P<0.01) in the 23- compared with the 6-month-old rats (7.95+/-0.70 versus 4.24+/-0.81; 1.91+/-0.10 versus 0.61+/-0.16; 0.58+/-0.09 versus 0.36+/-0.06 dyne/mm2x10(3), respectively). Active incremental circumferential arterial stiffness at 100 and 200 mm Hg was increased (P<0.01) in the older rats. In 6-month-old rats, activation of vascular smooth muscle enhanced (P<0.01) the incremental circumferential and axial stiffness measured at 200 mm Hg. In 23-month-old rats, only active incremental stiffness was increased (P<0.01) at 200 mm Hg. Aging increased (P<0.05) media thickness, collagen content, and the collagen/elastin ratio by 12%, 21%, and 38%, respectively. Elastin density and the number of smooth muscle cell nuclei were decreased by 20% and 31%, respectively, with aging. Thus, structural alterations that occur with aging are associated with changes in both active and passive stiffness. Vascular smooth muscle tone modulates arterial wall anisotropy differently during aging.

Effects of captopril on contractility after myocardial infarction: experimental observations.

After large myocardial infarction, compromised left ventricular (LV) function and changes in the peripheral circulation result in the syndrome of chronic congestive heart failure. Although treatment with angiotensin-converting enzyme inhibitors improve cardiovascular function, it is difficult to determine whether this benefit is due to changes in organ versus muscle function. The rat model of heart failure, created by ligating the left coronary artery, results in pathophysiology that is similar to that seen in patients, i.e., increased LV end-diastolic pressure and volume, hypertrophy of the noninfarcted myocardium, prolongation of the time constant of LV relaxation, decreased venous compliance, and increased total blood volume. In noninfarcted papillary muscles, isolated from rats with heart failure, maximal developed tension and peak rate of tension rise (+dT/dt) are decreased, time to peak tension is prolonged, and myocardial stiffness is increased. Morphologic changes include an increase in papillary muscle myocyte cross-sectional area and an increase in myocardial hydroxyproline content. Captopril (2 g/liter drinking water) alters LV loading by decreasing arterial pressure, increasing venous compliance, and decreasing blood volume. This results in a decrease in LV end-diastolic pressure and volume. In the noninfarcted myocardium, time to peak tension is shortened, whereas developed tension, +dT/dt, and muscle stiffness remain abnormal. Captopril decreases myocyte cross-sectional area, but collagen content remains elevated. Thus, in the rat infarct model of heart failure, treatment with captopril alters LV remodeling and hypertrophy but produces only modest improvement in muscle function.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic effects of direct angiotensin II blockade compared to converting enzyme inhibition in rat model of heart failure.

The purpose of this investigation was to compare the chronic effects of converting enzyme inhibition with captopril to direct blockade of angiotensin II (AII) with DuP 753 in the rat model of heart failure. Rats with chronic heart failure postinfarction were treated for 2 weeks with either captopril (2 g/L, N = 9) in their drinking water or with DuP 753 (40 mg/kg/day for two weeks by gastric gavage, N = 10), or placebo (N = 9). At this dose, DuP 753 shifted the log dose-pressor response curve to AII parallel to the right by two orders of magnitude in both chronically treated normal and heart failure rats. In rats with heart failure, DuP 753 and captopril reduced left ventricular end-diastolic pressure from 26.7 +/- 1.5 to 14.2 +/- 3.0 (P less than .01) and 15.8 +/- 2.2 mm Hg (P less than .05), respectively, left ventricular end-diastolic volume index from 2.71 +/- 0.10 to 2.03 +/- 0.17 (P less than .05) and 2.18 +/- 0.15 (P less than .05), respectively; venous compliance increased from 2.27 +/- 0.06 to 2.80 +/- 0.18 (P less than .05) and 3.02 +/- 0.21 mL/mm Hg/kg (P less than .01), respectively. There were no significant changes in left ventricular weight/body weight ratio, mean aortic pressure, heart rate, or right atrial pressure. There was a trend, but not significant, for a reduction in total blood volume from 65.8 +/- 1.1 to 59.4 +/- 3.0 and 64.9 +/- 3.9 mL/kg, respectively. Thus, direct blockade of AII with DuP 753 or with converting enzyme inhibition with captopril produces similar hemodynamic changes in rats with heart failure after myocardial infarction.

Studies on the use of thyroid hormone and a thyroid hormone analogue in the treatment of congestive heart failure.

In heart failure, cardiac output is insufficient to meet the needs of the body for oxygen delivery. Available data suggest that alterations in thyroid hormone metabolism may contribute to defective myocardial performance. Accordingly, thyroid hormone or a thyroid hormone analogue that improves cardiac performance might be useful in the treatment of heart failure and has been studied. Experimental and theoretical results of these studies are reviewed and indicate that thyroid hormone increases cardiac output by a combination of effects on the heart and peripheral circulation, specifically by increasing myocardial contractile performance and decreasing venous compliance. In the rat postinfarction model of heart failure, treatment with low doses of thyroxine (1.5 micrograms/100 g) for 3 days produced a positive inotropic response, including an increase in rate of change of left ventricular pressure and a decrease in left ventricular end-diastolic pressure. These changes could be attributed to conversion to triiodothyronine, the active intracellular form of thyroid hormone. When treatment with thyroxine was continued at the same or higher doses (3 to 15 micrograms/100 g) for 10 to 12 days, heart rate increased and improvement in left ventricular end-diastolic pressure was not sustained. More favorable results were obtained with 3,5-diiodothyropropionic acid, a cardiotonic thyroid hormone analogue administered at doses of 375 microgram/100 g, given in combination with captopril. Thus, triiodothyronine or a thyroid hormone analogue may be a useful adjunct to other measures in the treatment of heart failure.

Development of a thyroid hormone analogue for the treatment of congestive heart failure.

The possibility that thyroid hormone or a thyroid hormone analogue that improves cardiac performance might be useful in the treatment of heart failure has-been examined. In the rat postinfarction model of heart failure, treatment with low doses (1.5 micrograms/100 g) of thyroxine (T4) for 3 days produced a positive inotropic response, including an increase in left ventricular (LV) dP/dt and a decrease in LV end-diastolic pressure (LVEDP). When treatment with T4 was continued at the same or higher doses (3 to 15 micrograms/100 g) for 10-12 days, heart rate was increased and improvement in LVEDP was not sustained. To identify an analogue with a more favorable hemodynamic profile, single- and double-ring compounds related to T4 were screened for thyromimetic activity in heart cell cultures and for their ability to bind thyroid hormone receptors. One of the analogues selected, 3,5-diiodothyropropionic acid (DITPA), was found to have inotropic selectivity in hypothyroid rats. When administered (375 micrograms/100 g) to rats with ventricular dysfunction after myocardial infarction in combination with captopril, there was improvement of the resting and stressed cardiac index and LV filling pressure. Similar improvement in cardiac performance was obtained when DITPA was administered to rabbits after infarction. Thus a thyroid hormone analogue with inotropic selectivity may be a useful adjunct to other measures in the treatment of heart failure.

Rat infarct model of myocardial infarction and heart failure.

This review outlines the development and current use of the rat coronary artery ligation model of heart failure. The techniques to ligate the left coronary artery and to obtain morphologic/hemodynamic measurements are described. The authors show how the pathology seen in this model relates to clinical ischemic heart disease. An effort is made throughout the review to relate the changes that occur in this model to clinically relevant observations. For example, the progression to heart failure in these rats is similar to what happens when a patient sustains a large myocardial infarction, survives, but goes on to develop heart failure without another ischemic insult. In both rats and people with large infarctions, the noninfarcted myocardium, even though not damaged at the time of the infarct, cannot compensate sufficiently to prevent the eventual development of heart failure. In addition to being a good approximation of human disease, the responses to pharmacologic interventions, like angiotensin converting enzyme inhibitors, in rats has proved useful in predicting what will happen in humans given the same treatment. More recent data on the molecular control of ventricular remodeling emphasizes how this model will provide important information in the study of integrated physiology by examining biochemical, pharmacologic, and physiologic changes in the same tissue.

Large artery remodeling after myocardial infarction.

Rats with myocardial infarction (MI) after coronary artery ligation (n = 75) and sham operated rats (n = 40) were treated with captopril (2 g/l drinking water), hydralazine (80 mg/l drinking water), or untreated water for 3 wk. Arterial hemodynamics, carotid artery mechanical properties, and water permeability were measured. Arterial wall stress and interstitial fluid velocity were calculated. In infarcted rats, the characteristic impedance at matched pressure was increased by 135% (P < 0.02); captopril and hydralazine decreased characteristic impedance (P < 0.015). MI altered the material constants; captopril but not hydralazine normalized these constants. Water permeability was increased by 221% (P < 0.001) in infarcted rats; captopril but not hydralazine reversed water permeability (P < 0.05). MI resulted in a 59% increase (P < 0.05) in the arterial collagen area and a 22% decrease (P < 0.05) in the media thickness. Captopril but not hydralazine decreased (P < 0.03) collagen area. In conclusion, 1) arterial remodeling defined by alterations in the passive mechanical properties, water permeability, and structure occurs in rats after MI; and 2) captopril but not hydralazine reverses the arterial remodeling.

Chronic propranolol treatment promotes left ventricular dilation without altering systolic function after large myocardial infarction in rats.

In rats with chronic myocardial infarction (MI), we have examined the effects of prolonged beta-adrenergic blockade with propranolol on left ventricular (LV) performance, weight, and volumes. Sham-operated rats and rats with large MI (greater than 30%) were evaluated. Four groups of rats were studied: control, sham-operated (n = 12); control, MI (n = 12); propranolol (500 mg/L of drinking water)-treated, sham-operated (n = 10); and propranolol treated, MI (n = 10). Treatment was started 3 weeks after coronary ligation. After 5-6 weeks, LV, systemic arterial, and right atrial pressures in addition to aortic blood flow before and during volume loading were measured. LV pressure-volume relations were measured ex vivo. The rats with chronic MI demonstrated expected decreases in LV systolic performance and increased LV end-diastolic and right atrial pressures. Propranolol had no independent effect on LV systolic pressure, LV end-diastolic pressure, resting cardiac index, stressed cardiac index during volume loading, peak developed aortic pressure during aortic occlusion, or ejection fraction index in either sham-operated or infarcted rats; however, heart rate was decreased. LV weight/body weight was 2.17 +/- 0.04 mg/g in control sham-operated rats, which was not different from the propranolol-treated sham-operated rats (2.09 +/- 0.04 mg/g). The LV weight/body weight was increased (p less than 0.01) to 2.21 +/- 0.08 mg/g in the propranolol-treated MI group from 1.94 +/- 0.06 mg/g in the control MI group. The LV pressure-volume relation was not altered by propranolol in the sham-operated rats but was shifted to the right by MI.(ABSTRACT TRUNCATED AT 250 WORDS)

Selective vasopressin inhibition in rats with heart failure decreases afterload and results in venodilatation.

The hemodynamic effects of selective inhibition of arginine vasopressin (AVP) with a V1 antagonist, (CH2)5yreAVPa CL-1-4A, were studied in normal rats (n = 17) and in rats 4 weeks after coronary artery ligation with large myocardial infarctions and elevated left ventricular end-diastolic pressures (n = 22). In normal rats AVP inhibition with a 35-micrograms/kg bolus of AVP V1 antagonist did not change heart rate, right atrial, left ventricular systolic, left ventricular end-diastolic or aortic pressures. There were also no changes in mean circulatory filling pressure, unstressed vascular volume, blood volume or venous compliance. In rats with infarction and elevated left ventricular end-diastolic pressures, AVP inhibition did not change heart rate, right atrial pressure, mean circulatory filling pressure or blood volume, but mean aortic pressure decreased from 103 +/- 3 to 88 +/- 2 mm Hg (P less than .001), venous compliance increased (P less than .001) from 2.17 +/- 0.07 to 3.04 +/- 0.11 ml/mm Hg/kg and unstressed vascular volume decreased from 42.3 +/- 3.1 to 34.7 +/- 2.6 ml/kg (P less than .05). We conclude that inhibition of AVP with a specific V1 antagonist had no effect on the venous or arterial circulations in normal rats, but in rats with left ventricular dysfunction and heart failure after chronic myocardial infarction, AVP inhibition decreased arterial pressure and caused venodilatation.

Left ventricular function and remodeling after myocardial infarction in aging rats.

Adaptations of the aging left ventricle (LV) to hemodynamic overload are functionally and structurally distinct from those of the young organism. This study describes the influence of aging on LV hemodynamics and remodeling late after myocardial infarction (MI) in Fischer 344 Brown Norway rats. In sham rats at 23 mo, LV weight, myocyte cross-sectional area (CSA), and myocardial fibrosis were increased, whereas LV dP/dt, LV relaxation, and maximal LV systolic function declined with respect to younger rats (7, 12, and 18 mo of age). Isometric myocardial function was evaluated in papillary muscles of 12- and 23-mo-old sham rats. Myocardial systolic function was decreased in older rats. To determine how aging affects LV function and remodeling after MI, rats were infarcted at 7 and 18 mo of age and were studied 5 mo later. Infarct size was similar in each group. Right ventricular weight, LV end-diastolic pressure, and volume index were increased, whereas LV dP/dt, peak cardiac index, and peak developed LV pressure declined after MI. However, there were no significant differences between young and older rats in any variable of LV systolic function or remodeling after MI. Myocyte CSA increased in younger rats after MI but was unchanged in 23-mo-old rats. After MI, myocardial fibrosis was significantly increased from baseline only in younger rats. The negative interaction of aging and MI on myocyte hypertrophy and fibrosis was highly significant. The findings indicate that baseline LV and myocradial function decline with age. In the aging rat after MI, despite limited compensatory hypertrophy and more advanced baseline myocardial fibrosis, the long-term functional and structural adaptations to MI are similar to those of the mature adult heart.

Relative contribution of angiotensin II, bradykinin, and prostaglandins to the renal effects of converting enzyme inhibition in rats after chronic myocardial infarction.

We wished to determine whether enhanced bioavailability of bradykinin (BK) and vasodilatory prostaglandins contribute to renovascular and sodium-handling effects of angiotensin-converting enzyme (ACE) inhibition after myocardial infarction (MI). We studied rats after coronary artery ligation treated for 3 weeks with captopril or losartan (2 g/L drinking water for each agent). Hemodynamic and renal function studies were performed in conscious rats before and after sequential infusion BK inhibitor (BKI, 0.02 ng/kg/min) and indomethacin (1 mg/kg). Myocardial infarction increased filtration fraction (FF) 20% (p < .004) but did not change glomerular filtration rate (GFR), urine flow (UF), renal blood flow (RBF), renal vascular resistance (RVR), urine sodium (UNa), or fractional excretion of sodium (FENa). Captopril decreased (p < 0.001) mean arterial pressure (MAP) 25%, UF 61%, RVR 65%, and FENa 75% and increased (p < 0.05) GFR 22%, and RBF 34%. Losartan decreased (p < 0.05) MAP 27%, UF 52%, RVR 21%, and FENa 44%. In captopril-treated MI rats, BKI decreased (p < 0.05) GFR 22% and RBF 25% and increased (p < 0.05) RVR 32%, UNa 43%, and FENa 28%, whereas indomethacin decreased (p < 0.05) GFR 24% and increased (p < 0.05) UNa 86% and FENa 112%. In losartan-treated MI rats, BKI increased (p < 0.05) UNa 42% and FENa 60%, whereas indomethacin increased (p < 0.05) UNa 79% and FENa 85%. Activation of the BK and prostaglandin systems may play an important role in regulating renal function during chronic ACE inhibition, primarily by enhancing the renal vasodilatory effects of angiotensin II (AII) blockade.

Importance of venodilatation in prevention of left ventricular dilatation after chronic large myocardial infarction in rats: a comparison of captopril and hydralazine.

In rats with large myocardial infarctions, we compared the effects of captopril, a presumed arterial and venous vasodilator, with hydralazine, which is thought primarily to be an arterial vasodilator. To determine if the effects of captopril were dependent on the pathophysiological consequences of heart failure, we also studied a group of noninfarcted rats treated with captopril. In noninfarcted rats treated with captopril, left ventricular (LV) systolic and mean aortic pressures decreased from 132 +/- 12 to 107 +/- 15 mm Hg and 122 +/- 1 to 100 +/- 2, respectively (p less than 0.01). In noninfarcted rats, captopril decreased LV weight, LV weight/body weight, and total heart weight/body weight but produced no effects on the peripheral venous circulation. Rats subjected to coronary artery ligation were selected by ECG criteria to have large myocardial infarctions and were treated for 4 weeks with captopril (n = 8), hydralazine (n = 5), or placebo (n = 9). In infarcted rats treated with captopril, LV systolic, mean aortic pressures and LV end-diastolic pressure (LVEDP) decreased (p less than 0.01) from 115 +/- 4 to 86 +/- 3 mm Hg, 106 +/- 4 to 74 +/- 3 mm Hg, and 23 +/- 2 to 11 +/- 2 mm Hg, respectively. Mean circulatory filling pressure decreased (p less than 0.05) from 11.2 +/- 0.6 to 8.7 +/- 0.8 mm Hg and venous compliance increased (p less than 0.05) from 2.04 +/- 0.07 to 2.70 +/- 0.20 ml/mm Hg/kg. Blood volume decreased (p less than 0.05) from 67.3 +/- 0.9 to 58.2 +/- 1.8 ml/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Captopril restores hemodynamic responsiveness to atrial natriuretic peptide in rats with heart failure.

Atrial natriuretic peptide levels are elevated in heart failure. However, the hemodynamic responses to exogenous atrial natriuretic peptide infusion in heart failure are blunted. To determine if captopril can restore hemodynamic responsiveness to atrial natriuretic peptide infusion in rats with heart failure, studies were performed in a rat model of heart failure after coronary artery ligation. Rats with heart failure received either captopril (2 g/l drinking water) or placebo for 4 weeks and then were treated with an infusion of atrial natriuretic peptide (0.3 microgram/kg/min). Captopril treatment alone improved hemodynamics. Left ventricular end-diastolic pressure, mean aortic pressure, and mean circulatory filling pressure decreased from 22 +/- 2 to 14 +/- 1, from 106 +/- 4 to 76 +/- 3, and from 10.5 +/- 0.6 to 8.8 +/- 0.4 mm Hg, respectively. Heart rate, right atrial pressure, and hematocrit were unchanged. Total blood volume decreased from 66.0 +/- 1.0 to 60.0 +/- 1.0 ml/kg; venous compliance increased from 2.1 +/- 0.1 to 2.7 +/- 0.1 ml/kg/mm Hg. Atrial natriuretic peptide alone had minimal hemodynamic effects on rats with heart failure. There was no change in right atrial pressure, mean aortic pressure, left ventricular end-diastolic pressure, mean circulatory filling pressure, and total blood volume. However, atrial natriuretic peptide infusion increased venous compliance from 2.1 +/- 0.1 to 2.4 +/- 0.1 ml/kg/mm Hg. Heart rate and hematocrit increased from 323 +/- 5 to 359 +/- 8 beats/min and from 48 +/- 1% to 51 +/- 1%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Serial changes in left ventricular relaxation and chamber stiffness after large myocardial infarction in rats.

To determine the time course of changes in left ventricular diastolic properties after a large myocardial infarction, we serially measured left ventricular relaxation, chamber stiffness, and the ratio of left ventricular cavity to wall volume (V/VW) after coronary artery ligation in rats. Left ventricular relaxation was measured during the occlusion and then both relaxation and chamber stiffness were measured at 3 hr, 24 hr, and 3, 5, and more than 22 days after infarction. Left ventricular pressures and left ventricular dP/dt were recorded with micromanometer-tipped catheters. Left ventricular relaxation was measured by computer digitization of the left ventricular pressure tracings and averaged over 100 to 150 cardiac cycles. Five chamber stiffness constants were calculated from pressure-volume curves that were obtained ex vivo. We found ventricular relaxation prolonged for the first hour after coronary occlusion; relaxation was maximally prolonged at 10 to 15 min after onset of occlusion. After 1 hr relaxation returned to normal. However, by 5 days ventricular relaxation was again prolonged. Left ventricular stiffness constants were increased at 3 and 24 hr, resulting in a shift of the left ventricular pressure-volume relation to the left. At 3 days after coronary artery ligation, all stiffness constants and the pressure-volume relation returned to normal. At more than 22 days the pressure-volume relation was shifted to the right and the stiffness constant for low filling pressures was decreased. V/VW was significantly decreased from 0.603 +/- 0.021 at 3 and 24 hr to 0.379 +/- 0.024 and 0.362 +/- 0.032, respectively. V/VW was significantly increased at more than 22 days (0.921 +/- 0.094).(ABSTRACT TRUNCATED AT 250 WORDS)