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Biomedical subjects

J G Mill

Publications and source records attributed to J G Mill.

At least 19 recordsLinked to original sources
PubMed2006

Endothelial nitric oxide synthase gene variant modulates the relationship between serum cholesterol levels and blood pressure in the general population: new evidence for a direct effect of lipids in arterial blood pressure.

BACKGROUND: A causal relationship between plasma cholesterol and blood pressure remains poorly understood. It has been postulated that the decrease in nitric oxide (NO) availability is a potential mechanism by which hypercholesterolemia may stimulate blood pressure elevation. However, evidence supporting the role of the L-arginine-NO pathway on the relationship between hypertension and hypercholesterolemia is still lacking. METHODS AND RESULTS: We tested for an association of the expressed NO synthase (eNOS) Glu298Asp gene variant and plasma levels of lipids and lipoproteins in the determination of systolic blood pressure levels in a 1577 individuals randomly selected from the general population. Significant interactions could be disclosed either between the Glu298Asp gene variant and total-cholesterol (p = 0.02), log-transformed triglycerides (p = 0.004) or non-HDL-cholesterol (p = 0.003) in the determination of systolic blood pressure. In addition, although the presence of the AspAsp genotype did not significantly increase the risk of hypertension in individuals in the 50% lowest percentile of total-cholesterol, presence of this genotype significantly increased the risk of hypertension in individuals in the 50% highest percentile. Finally, in a multiple logistic regression model adjusting for age, sex, diabetes, ethnicity, smoking status and BMI, the AspAsp genotype significantly increased the risk of hypertension only in individuals with total-cholesterol above 209 mg/dL (p = 0.05, odds ratios (OR) = 2.0). CONCLUSION: Taken together, these results provide evidence supporting the role of the eNOS Glu298Asp gene variant in modulating blood pressure through a relationship with lipid levels.

Adult↗
PubMed2004

Chronic experimental myocardial infarction produces antinatriuresis by a renal nerve-dependent mechanism.

The present study focused on the role of sympathetic renal nerve activity, in mediating congestive heart failure-induced sodium retention following experimental chronic myocardial infarction. Groups of male Wistar rats (240-260 g) were studied: sham-operated coronary ligation (CON3W, N = 11), coronary ligation and sham-operated renal denervation (INF3W, N = 19), 3 weeks of coronary ligation and sympathetic renal nerve denervation (INF3WDX, N = 6), sham-operated coronary ligation (N = 7), and 16 weeks of coronary ligation (INF16W, N = 7). An acute experimental protocol was used in which the volume overload (VO; 5% of body weight) was applied for 30 min after the equilibration period of continuous iv infusion of saline. Compared to control levels, VO produced an increase (P < 0.01, ANOVA) in urine flow rate (UFR; 570%) and urinary sodium excretion (USE; 1117%) in CON3W. VO induced a smaller increase (P < 0.01) in USE (684%) in INF3W. A similar response was also observed in INF16W. In INF3WDX, VO produced an immediate and large increase (P < 0.01) in UFR (547%) and USE (1211%). Similarly, in INF3W VO increased (P < 0.01) UFR (394%) and USE (894%). Compared with INF3W, VO induced a higher (P < 0.01) USE in INF3WDX, whose values were similar to those for CON3W. These results suggest that renal sympathetic activity may be involved in sodium retention induced by congestive heart failure. This premise is supported by the observation that in bilaterally renal denervated INF3WDX rats myocardial infarction was unable to reduce volume expansion-induced natriuresis. However, the mechanism involved in urinary volume regulation seems to be insensitive to the factors that alter natriuresis.

Animals↗
PubMed2001

Ambulatory blood pressure and Doppler echocardiographic indexes of borderline hypertensive men presenting an exaggerated blood pressure response during dynamic exercise.

Borderline hypertension (BH) has been associated with an exaggerated blood pressure (BP) response during laboratory stressors. However, the incidence of target organ damage in this condition and its relation to BP hyperreactivity is an unsettled issue. Thus, we assessed the Doppler echocardiographic profile of a group of BH men (N = 36) according to office BP measurements with exaggerated BP in the cycloergometric test. A group of normotensive men (NT, N = 36) with a normal BP response during the cycloergometric test was used as control. To assess vascular function and reactivity, all subjects were submitted to the cold pressor test. Before Doppler echocardiography, the BP profile of all subjects was evaluated by 24-h ambulatory BP monitoring. All subjects from the NT group presented normal monitored levels of BP. In contrast, 19 subjects from the original BH group presented normal monitored BP levels and 17 presented elevated monitored BP levels. In the NT group all Doppler echocardiographic indexes were normal. All subjects from the original BH group presented normal left ventricular mass and geometrical pattern. However, in the subjects with elevated monitored BP levels, fractional shortening was greater, isovolumetric relaxation time longer, and early to late flow velocity ratio was reduced in relation to subjects from the original BH group with normal monitored BP levels (P<0.05). These subjects also presented an exaggerated BP response during the cold pressor test. These results support the notion of an integrated pattern of cardiac and vascular adaptation during the development of hypertension.

Adult↗
PubMed2000

Reduction in left ventricular hypertrophy in hypertensive patients treated with enalapril, losartan or the combination of enalapril and losartan.

OBJECTIVE: To compare the regression of left ventricular hypertrophy in patients with moderate hypertension treated with enalapril, losartan or a combination of the two drugs at lower doses. METHODS: Patients of both sexes with moderate hypertension confirmed by ambulatory monitoring of arterial blood pressure and with left ventricular hypertrophy on echocardiogram were assigned to three groups: enalapril (35 mg/day, n=15), losartan (175 mg/day, n=15) and enalapril losartan (15 mg+100 mg/day, n=16). The patients received the drugs for 10 months. RESULTS: The three therapeutic regimens were equally effective in reducing blood pressure and left ventricular mass index (LVMI, g/m2): 141+/-3.9 to 123+/-3.6 in the enalapril group (p<0.05), from 147+/-3.8 to 133+/-2.8 in the losartan group (p<0.05), and from 146+/-3.0 to 116+/-4.0 in the enalapril+losartan group (p<0.05). However, the percent reduction of LVMI was significantly greater (p<0.01) in the enalapril+losartan group (20.5+/-5.0%) than in enalapril (12.4+/-3.2%) and the losartan (9.1+/-2.1%) groups. Normalization of LVMI was obtained in 10 out of the 16 patients who received enalapril+ losartan, in 6 out of the 15 patients who received only enalapril and in 4 out of the 15 patients treated with losartan. CONCLUSION: The combination of an angiotensin-converting enzyme inhibitor and an angiotensin II receptor antagonist (AT1 receptor antagonist) in patients produced an additional effect on the reduction of left ventricular hypertrophy. This finding may depend on a more complete inhibition of the cardiac renin-angiotensin.

Adult↗
PubMed1999

Racial differences in aortic stiffness in normotensive and hypertensive adults.

OBJECTIVE: To investigate whether differences exist in the mechanical properties of large arteries between white and black subjects. DESIGN: Eighty-two white (49 normotensive and 33 untreated hypertensive) and 38 black (24 normotensive and 14 untreated hypertensive) adult male volunteers were studied in a cross-sectional study. METHODS: Carotid-femoral pulse wave velocity was measured as an index of arterial stiffness, using a recently developed non-invasive automatic device, and compared between white and black subjects before and after the adjustment for age. The slope of regressions for pulse wave velocity and systolic blood pressure were also compared between racial groups. RESULTS: In the normotensive group, white subjects presented higher mean values of pulse wave velocity than blacks while the opposite behavior was found in the hypertensive group. After adjustment for age, significant differences in pulse wave velocity between whites and blacks became evident in the normotensive (whites 8.15 +/- 0.04 versus blacks 7.75 +/- 0.02 m/s; P < 0.001) and hypertensive (whites 8.88 +/- 0.02 versus blacks 9.30 +/- 0.17 m/s; P < 0.001) groups. Linear regression analysis for age-adjusted pulse wave velocity and systolic blood pressure showed that the slope was significantly greater in blacks than in whites (0.040 +/- 0.002 versus 0.019 +/- 0.001 m/s; P < 0.001). CONCLUSION: These data indicate that there is a greater pressure-dependent increase in aortic stiffness in blacks than in whites. This finding points towards major differences in mechanical properties of large arteries between these racial groups.

Adult↗
PubMed1999

Differential effects of isoproterenol on the activity of angiotensin-converting enzyme in the rat heart and aorta.

The excessive stimulation of beta-adrenergic receptors in the heart induces myocardial hypertrophy. There are several experimental data suggesting that this hypertrophy may also depend, at least partially, on the increase of local production of angiotensin II secondary to the activation of the cardiac renin-angiotensin system. In this study we investigated the effects of isoproterenol on the activity of angiotensin-converting enzyme (ACE) in the heart and also in the aorta and plasma. Male Wistar rats weighing 250 to 305 g were treated with a dose of (+/-)-isoproterenol (0.3 mg kg-1 day-1, N = 8) sufficient to produce cardiac hypertrophy without deleterious effects on the pumping capacity of the heart. Control rats (N = 7) were treated with vehicle (corn oil). The animals were killed one week later. ACE activity was determined in vitro in the four cardiac chambers, aorta and plasma by a fluorimetric assay. A significant hypertrophy was observed in both ventricular chambers. ACE activity in the atria remained constant after isoproterenol treatment. There was a significant increase (P < 0.05) of ACE activity in the right ventricle (6.9 +/- 0.9 to 8.2 +/- 0.6 nmol His-Leu g-1 min-1) and in the left ventricle (6.4 +/- 1.1 to 8.9 +/- 0.8 nmol His-Leu g-1 min-1). In the aorta, however, ACE activity decreased (P < 0.01) after isoproterenol (41 +/- 3 to 27 +/- 2 nmol His-Leu g-1 min-1) while it remained unchanged in the plasma. These data suggest that ACE expression in the heart can be increased by stimulation of beta-adrenoceptors. However, this effect is not observed on other local renin-angiotensin systems, such as the aorta. Our data also suggest that the increased sympathetic discharge and the elevated plasma concentration of catecholamines may contribute to the upregulation of ACE expression in the heart after myocardial infarction and heart failure.

Adrenergic beta-Agonists↗
PubMed1999

Effects of mercury on the arterial blood pressure of anesthetized rats.

The available data suggests that hypotension caused by Hg2+ administration may be produced by a reduction of cardiac contractility or by cholinergic mechanisms. The hemodynamic effects of an intravenous injection of HgCl2 (5 mg/kg) were studied in anesthetized rats (N = 12) by monitoring left and right ventricular (LV and RV) systolic and diastolic pressures for 120 min. After HgCl2 administration the LV systolic pressure decreased only after 40 min (99 +/- 3.3 to 85 +/- 8.8 mmHg at 80 min). However, RV systolic pressure increased, initially slowly but faster after 30 min (25 +/- 1.8 to 42 +/- 1.6 mmHg at 80 min). Both right and left diastolic pressures increased after HgCl2 treatment, suggesting the development of diastolic ventricular dysfunction. Since HgCl2 could be increasing pulmonary vascular resistance, isolated lungs (N = 10) were perfused for 80 min with Krebs solution (continuous flow of 10 ml/min) containing or not 5 microM HgCl2. A continuous increase in pulmonary vascular resistance was observed, suggesting the direct effect of Hg2+ on the pulmonary vessels (12 +/- 0.4 to 29 +/- 3.2 mmHg at 30 min). To examine the interactions of Hg2+ and changes in cholinergic activity we analyzed the effects of acetylcholine (Ach) on mean arterial blood pressure (ABP) in anesthetized rats (N = 9) before and after Hg2+ treatment (5 mg/kg). Using the same amount and route used to study the hemodynamic effects we also examined the effects of Hg2+ administration on heart and plasma cholinesterase activity (N = 10). The in vivo hypotensive response to Ach (0.035 to 10.5 microg) was reduced after Hg2+ treatment. Cholinesterase activity (microM h-1 mg protein-1) increased in heart and plasma (32 and 65%, respectively) after Hg2+ treatment. In conclusion, the reduction in ABP produced by Hg2+ is not dependent on a putative increase in cholinergic activity. HgCl2 mainly affects cardiac function. The increased pulmonary vascular resistance and cardiac failure due to diastolic dysfunction of both ventricles are factors that might contribute to the reduction of cardiac output and the fall in arterial pressure.

Animals↗
PubMed1998

Comparison of the contractile performance of the hypertrophied myocardium from spontaneous hypertensive rats and normotensive infarcted rats.

The sarcoplasmic reticulum (SR) exerts a key role on the excitation-contraction coupling process in the myocardium. Since the relation between the volume of cellular organelles, such as SR, and the sarcolemmal area of myocytes is not uniform in myocardial hypertrophy of different etiologies, we compared the contractile performances of hypertrophied left ventricular papillary muscles from rats with pressure overload and with volume overload. Hemodynamically compensated spontaneous hypertensive rats (SHR, 3 months old, systolic blood pressure = 189 +/- 4 mmHg, n = 8) and Wistar rats with healed (30 days) myocardial infarction (MI, n = 7) produced by ligation of the left coronary artery were used. Results were compared with age-matched Wistar control (CON) rats (n = 13). Force (F), corrected to muscle cross-sectional area (g/mm2), and dF/dt were recorded in muscles contracting isometrically and stretched to Lmax. The inotropic response to increasing extracellular Ca2+ concentrations (1.25 to 5.0 mM) was compared in twitches (0.5 Hz) and during tetanic stimulation (5 Hz, 30 s) in the muscles treated with 1 microM ryanodine. F recorded in basal conditions (Ca = 1.25 mM, 0.5 Hz) in the CON group (1.34 +/- 0.20 g/mm2) was higher (p < 0.05) than in the MI (0.73 +/- 0.13 g/mm2) and lower (p < 0.05) than in the SHR group (2.08 +/- 0.25 g/mm2). Similar differences between groups were also observed in relation to +dF/dt. Increasing extracellular Ca produced a parallel increase of F and +dF/dt in the three groups of muscles. Ryanodine treatment reduced F and +dF/dt in all groups and completely inhibited the development of force in post-rest contractions, indicating SR inhibition. SHR muscles were more sensitive to ryanodine than CON and MI (F decrease = 64 +/- 7, 51 +/- 5, and 22 +/- 5%, respectively, p < 0.05). The tetanic tension (Ca = 1.25 mM) was similar in SHR and CON (0.82 +/- 0.19 and 0.92 +/- 0.18 g/mm2; p > 0.05) and depressed in the MI group (0.35 +/- 0.12 g/mm2). These data suggest an increased participation of SR as source of activator Ca in the hypertrophied muscle of SHR. This adaptation likely contributes to maintain the normal cardiac function in hemodynamically compensated SHR, despite increasing afterload levels. This adaptation seems not to occur after MI, which may contribute to the depressed contractile performance of the left ventricular muscle surviving to infarction.

Animals↗
PubMed1997

Bezold-Jarisch reflex in myocardial infarcted rats.

The Bezold-Jarisch reflex (BJR), produced by the administration of 5-hydroxytryptamine (5-HT, 4-16 micrograms/kg, iv), was evaluated in awake rats bearing short- (1 day) or long-term (30 days) myocardial infarction. Heart chronotropic response produced by acetylcholine was further assessed by Langendorff's isolated heart perfusion technique. Compared to the sham-operated group, infarcted rats showed either hypotension and tachycardia or bradycardia following short- or long-term myocardial infarction, respectively. Whereas the long-term myocardial infarction attenuated 5-HT-induced hypotension and bradycardia by about -25 and -80%, respectively, no significant response changes were observed in short-term infarcted rats. Impairment of BJR correlated significantly (P < 0.01) with the extent of myocardial necrosis in the 30-days infarcted group. Chronotropic responsiveness of the heart to acetylcholine in infarcted rats did not differ from the sham-operated group. Transmural antero-medio-lateral infarcted areas spanned over nearly 37% (1-day group) and 35% (30-days group) of the left ventricular circumference. These results indicate that cardioinhibitory and vasodepressor reflex responses to 5-HT are significantly impaired in chronic myocardial infarction associated with (1) marked hypertrophy of left atrium and/or of non-infarcted left ventricle, which are the main origin of vagal chemosensitive C-fibers, (2) morphological damage of this innervation due to the necrotic injury of the left ventricle, (3), possible attenuation in the vagal afferents located in the lungs and/or (4) enhancement of the chemical sensitivity of cardiac sympathetic afferents.

Animals↗
PubMed1997

Effects of captopril on interstitial collagen in the myocardium after infarction in rats.

BACKGROUND: Myocardial infarction is an important cause of heart failure because it cause tissue loss and contractility disturbances. In chronically infarcted hearts the increase in the collagen content in the extracellular matrix of the surviving viable myocardium has been considered a major factor contributing to development of heart failure. Postinfarction neuroendocrine activation involving the renin-angiotensin system has been implicated in this cardiac fibrosis. METHODS AND RESULTS: As collagen synthesis and degradation are dynamic processes and postinfarction remodeling is a time-dependent phenomenon, rats submitted to coronary artery ligation to produce myocardial infarction were treated with captopril after infarction (30 mg/kg, intraperitoneally, daily) to investigate whether blockade of the renin-angiotensin system can prevent postinfarction myocardial hypertrophy and reactive fibrosis. Groups of rats with myocardial infarction were treated with captopril throughout the protocol period (6 weeks), or during the first 3 weeks after infarction (early therapy), or only during the last 3 weeks of the protocol (late therapy). Untreated groups of rats with or without myocardial infarction were used as control subjects. All animals were killed 6 weeks after surgery to evaluate hypertrophy of heart chambers and collagen deposition in the right ventricle wall and in surviving left ventricular muscle. Protein and hydroxyproline concentrations were assayed biochemically in these tissue homogenates. Only rats with an infarct covering 20 to 40% of the left ventricular surface were included in the study. In the control uninfarcted group (n = 12), hydroxyproline content was 152 +/- 12 micrograms in the right ventricle and 370 +/- 30 micrograms in the left ventricle. These values increased (P < .05) to 232 +/- 13 and 630 +/- 46 micrograms, respectively, in the group with myocardial infarction (n = 8) without treatment. These values were significantly reduced (P < .05) to 160 +/- 9 micrograms in the right ventricle and 520 +/- 40 micrograms in the left ventricle in the group with myocardial infarction treated with captopril for 6 weeks. The percentage decreases in collagen content and myocardial weight produced by captopril were similar. Thus, hydroxyproline concentration (mg hydroxyproline muscle), which increases significantly in both ventricles after myocardial infarction, was not modified by captopril therapy. Protein concentration in the right and left ventricular muscles decreased after myocardial infarction. This decrease was enhanced in the infarcted groups submitted to captopril treatment, mainly in the group treated for 6 weeks. Lesser effects on hypertrophy and hydroxyproline content were observed in the groups of rats treated with captopril in only the earlier or later phase of infarction. CONCLUSIONS: It is concluded that captopril reduces similarly postinfarction hypertrophy and collagen deposition in surviving myocardium. These effects, although less intense, also occur when the drug is used for a short period immediately after myocardial infarction or when used later, when ventricular remodeling is almost fully developed.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

[Activation of the cardiac angiotensin-converting enzyme after myocardial infarction and its role in ventricular remodeling].

PURPOSE: To determine angiotensin converting enzyme (ACE) activity in the heart of infarcted rats and to investigate the effects of captopril and losartan on the post-infarction remodeling process. METHODS: Myocardial infarction (MI) was produced in Wistar rats by ligature of the left coronary artery. Control rats (Con) underwent a sham surgery. MI and Con rats remained untreated or were treated with captopril (30 mg/kg/day) or losartan (15 mg/kg/day) for 30 days. ACE activity was determined in right (RV) and left ventricular (LV) muscles and in the scar tissue. The effects of captopril therapy was also investigated in the hydroxiproline (OH-Pro) and protein in RV and LV. RESULTS: ACE activity increased 25% in the RV and 70% in the remaining LV muscle. The highest ACE activity was found in the scar tissue, where it was 4.5 times the value of the LV muscle (420 +/- 68 vs 94 +/- 8 nmoles/g/min; P < 0.01). An increase of the end-diastolic pressure and of the muscle mass was found in the RV and LV of MI rats. Captopril and losartan treatments were equally efficient to attenuate these parameters in both ventricles. Captopril also reduced the total OH-Pro content in the RV and LV muscles. The Prot concentration was significantly reduced in the myocardium of MI rats, an effect enhanced by captopril therapy. CONCLUSION: The AII concentration in the blood draining from the scar to the surrounding muscle is probably high. It is likely that this elevated local generation of AII contributes to hypertrophy and to collagen deposition. The effects of ACE inhibitors on remodeling are likely to depend on the reduction of the locally generated AII.

Angiotensin II↗
PubMed1997

Increased angiotensin-converting enzyme activity in the left ventricle after infarction.

An increase in angiotensin-converting enzyme (ACE) activity has been observed in the heart after myocardial infarction (MI). Since most studies have been conducted in chronically infarcted individuals exhibiting variable degrees of heart failure, the present study was designed to determine ACE activity in an earlier phase of MI, before heart failure development. MI was produced in 3-month old male Wistar rats by ligation of the anterior branches of the left coronary artery, control rats underwent sham surgery and the animals were studied 7 or 15 days later. Hemodynamic data obtained for the anesthetized animals showed normal values of arterial blood pressure and of end-diastolic pressure in the right and left ventricular cavities of MI rats. Right and left ventricular (RV, LV) muscle and scar tissue homogenates were prepared to determine ACE activity in vitro by measuring the velocity of His-Leu release from the synthetic substrate Hyp-His-Leu. ACE activity was corrected to the tissue wet weight and is reported as nmol His-Leu g-1 min-1. No significant change in ACE activity in the RV homogenates was demonstrable. A small nonsignificant increase of ACE activity (11 +/- 9%; P > 0.05) was observed 7 days after MI in the surviving left ventricular muscle. Two weeks after surgery, however, ACE activity was 46 +/- 11% (P < 0.05) higher in infarcted rats compared to sham-operated rats. The highest ACE activity was demonstrable in the scar tissue homogenate. In rats studied two weeks after surgery, ACE activity in the LV muscle increased from 105 +/- 7 nmol His-Leu g-1 min-1 in control hearts to 153 +/- 11 nmol His-Leu g-1 min-1 (P < 0.05) in the remaining LV muscle of MI rats and to 1051 +/- 208 nmol His-Leu g-1 min-1 (P < 0.001) in the fibrous scar. These data indicate that ACE activity increased in the heart after infarction before heart failure was demonstrable by hemodynamic measurements. Since the blood vessels of the scar drain to the remaining LV myocardium, the high ACE activity present in the fibrous scar may increase the angiotensin II concentration and decrease bradykinin in the cardiac tissues surrounding the infarcted area. The increased angiotensin II in the fibrous scar may contribute to the reactive fibrosis and hypertrophy in the left ventricular muscle surviving infarction.

Angiotensin II↗
PubMed1997

Doppler echocardiographic indexes and 24-h ambulatory blood pressure data in sedentary middle-aged men presenting exaggerated blood pressure response during dynamical exercise test.

Previous studies have pointed out that exaggerated blood pressure (BP) response during physical exercise could be an early marker of essential hypertension. Apparently some of the exaggerated BP responders present changes in the heart geometry and function that are usually found in the early course of the hypertensive disease. To evaluate the association between exaggerated BP response and these changes, we submitted 20 normotensive men presenting elevated BP response during bicycle exercise (hyperreactive group, systolic BP > or = 220 mmHg at maximal workload) to 24-h ambulatory blood pressure monitoring (ABPM) and to two-dimensionally guided M-mode echocardiography and pulsed Doppler. The results from this group were contrasted with those of a comparable group, which otherwise, presented normal BP response during the same procedure (control group, systolic BP < or = 210 mmHg at maximal workload). The ABPM measurements were normal and analogous between the two groups: the mean 24-h systolic blood pressure (SBP) was respectively 126 +/- 6 mmHg and 129 +/- 5 mmHg, diastolic blood pressure (DBP) 82 +/- 4 mmHg in both groups, and heart rate (HR), respectively 76 +/- 9 and 74 +/- 7 bpm. The univariate correlation (R) between the maximal BP response during bicycle exercise and BP measurements in the ABPM were in general weak, and as a whole, the hyperreactive group presented the weakest correlation coefficients. M-mode echocardiographic data such as the left ventricular mass index (LVMI, 80 +/- 10 vs. 81 +/- 11 g/m2), posterior wall and interventricular septal thickness (PWT, 8.8 +/- 0.6 vs. 8.6 +/- 0.7 mm; IVST, 9.0 +/- 0.4 vs. 8.8 +/- 0.6) were also normal and comparable between the groups. LV systolic functional indexes such as fractional shortening (LVFS, 39 +/- 2.8 vs. 40 +/- 3.5%) and ejection fraction (LVEF, 70 +/- 3.5 vs. 71 +/- 3.7%) were also normal and similar. Doppler-derived LV diastolic functional indexes such as the peak velocity of early flow divided by the peak velocity of late flow (RE/A) and isovolumetric relaxation time (IVRT) were also equivalent (RE/A, both 1.3 +/- 0.2, IVRT 79 +/- 7 vs. 81 +/- 6 msec). These results support the concept that an exaggerated BP elevation during physical activity, when not accompanied of higher levels of BP during daily activities are not associated with changes in the heart geometry or in the ventricular function, and might represent an hemodynamical behavior of limited pathological and clinical importance. These conclusions must be taken cautiously since personal characteristics such as life style, family history of hypertension, gender, race and also the levels of BP chosen to delimit a normal and an exaggerated BP response might be important factors determining the consequences of the hyperreactive behavior.

Adult↗
PubMed1996

Cardiac baroreflex properties in myocardial infarcted rats.

Recent studies demonstrated that chronic but not acute myocardial infarction impairs the cardiopulmonary reflex. The aim of the present study was to evaluate the baroreflex in awake rats bearing short-term (1 day) or long-term (30 days) myocardial infarction. Left ventricular infarction was produced by ligation of the anterior descending branch of the left coronary artery. In order to examine the baroreceptor reflex function by means of sigmoidal curvefitting analysis in conscious rats, reflex heart rate responses were elicited by alternate intravenous injections of phenylephrine (change, +5 to +40 mmHg) and sodium nitroprusside (change, -5 to -40 mmHg). Infarcted rats showed either hypotension plus tachycardia (1 day) or bradycardia (30 days) in resting conditions. The baroreceptor reflex gain (sensitivity) was significantly increased in 30 days (5.20 +/- 0.33 bpm/mmHg, p < 0.01) but not in 1 day (3.78 +/- 0.20 bpm/mmHg) infarcted rats when compared to sham rats (3.83 +/- 0.16 bpm/mmHg). Transmural antero-medio-lateral infarcted areas spanned over nearly 37% (1 day group) and 35% (30 days group) of the left ventricular circumference. Myocardial hypertrophy was showed in right ventricle (39%, p < 0.01) as well as in right (35%, P < 0.05) and left atria (127%, p < 0.001) in the 30 days but not in the 1 day infarcted group. The enhancement of baroreflex correlated significantly with the extent of myocardial necrosis in the 30 days infarcted group. We conclude that baroreflex control of heart rate is well preserved in short- but exaggerated in long-term myocardial infarction. The enhancement of the baroreflex gain could reflect a compensatory mechanism to the impairment of the cardiopulmonary reflex following chronic myocardial infarction and thus contributing to sustain the arterial pressure and heart rate in low levels.

Animals↗
PubMed1995

Ventricular action potential and L-type calcium channel in infarct-induced hypertrophy in rats.

INTRODUCTION: The present investigation was aimed at characterization of: (1) action potential parameters; and (2) L-type calcium channels in the hypertrophied ventricular tissue surviving an extensive healed myocardial infarction in the rat. METHODS AND RESULTS: Myocardial infarction was produced in Wistar rats by ligation of the left coronary artery. One to 2 months later, their hearts were subjected to electrophysiologic study. The main difference in subendocardial transmembrane potentials recorded with intracellular microelectrodes was an increase in action potential duration (APD). In the left ventricle, the infarcted/sham-operated APD ratio ranged from 2.7 to 7.2, whereas in the right ventricle it ranged from 1.6 to 2.3 in different regions. When compared with control cells, ventricular myocytes from infarcted hearts were found to be larger (P < 0.01) and showed a reduction (P < 0.05) in L-type calcium current (LCa,L) density obtained by whole cell, patch clamp (at 0 mV: 4.44 +/- 0.41 in infarcted vs 8.03 +/- 1.22 pA/pF in normal). The time course of decay of the currents could be fitted by two exponential functions in both normal and infarcted hearts. There was a tendency toward an increase in the time constant of the slower component of inactivation, tau 2, significant only at +20 mV (215 +/- 25 vs 151 +/- 15 msec). CONCLUSIONS: Cardiac hypertrophy of healed infarction in rats is associated with lengthening of the action potential in both ventricles. The main alteration observed in ICa,L was a decrease in the current density. Thus, alteration of the calcium channel is not the determinant factor of APD increase.

Action Potentials↗
PubMed1995

Characteristics of tetanic contractions in caffeine-treated rat myocardium.

Skinned fiber preparations are used to obtain the maximal contractile activation of isolated myocardial preparations. Tetanic contractions elicited in the presence of sarcoplasmic reticulum inhibitors have also been used as an alternative method to produce maximal active tension in the intact myocardium. In this work our purpose was to define the best conditions to obtain tetanic contractions in the rat myocardium and to compare the influence of muscle length and inotropic interventions (Ca2+ and Bay K 8644) in the tension produced in twitches and tetanic contractures. Papillary muscles were mounted in a perfusion chamber to record isometric force. Tetanic contractions were elicited by using suprathreshold stimulation with rectangular pulses (10 ms duration) at 5 Hz in the presence of 2.5 mM caffeine. Caffeine depressed the twitch tension but the tetanic tension was similar to that produced under steady-state stimulation (0.5 Hz) in control conditions. Tetanic and twitch tensions were similar along the whole extension of the length-tension curve and under the positive inotropic effects produced by Ca2+ (0.25 to 3.75 mM) or by the Ca(2+)-channel agonist Bay K 8644 (1 microM). During long tetanic stimuli (60 s) a time-dependent tension decay was observed. This decay was prolonged by reducing the extracellular K+ from 5.4 to 1.0 microM, suggesting that Ca2+ extrusion through the Na-Ca exchanger seems to occur during tetanic stimulation. Since tetanic tension was never higher than the tension obtained in twitches elicited at the same Ca2+ concentration (0.5 Hz), we conclude that tetanic contractures represent a useful tool to investigate the contractile response of intact myocardial preparations with a nonfunctional sarcoplasmic reticulum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗