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Biomedical subjects

K B Ramanathan

Publications and source records attributed to K B Ramanathan.

At least 37 records · Page 2Linked to original sources
PubMed1989

Dilevalol in severe hypertension. A multicenter trial of bolus intravenous dosing.

Dilevalol, the R-R optical isomer of labetalol, a nonselective beta-antagonist with vasodilation from selective beta 2 agonism, was administered in sequential multiple bolus intravenous injections of 10 to 100 mg in total doses ranging from 35 to 585 mg (mean dose, 414 mg) to 101 patients with supine diastolic blood pressures above 120 mm Hg. Mean blood pressure was reduced from 200 (+/- 3)/129 (+/- 1) mm Hg to 149 (+/- 2)/101 (+/- 1) mm Hg, a mean reduction of 51/28 mm Hg. The therapeutic goal was established as a reduction in supine diastolic blood pressure to less than 100 mm Hg or a reduction of at least 30 mm Hg. This was achieved in 62 (61%) of 101 patients, with an additional 7 patients having a final supine diastolic blood pressure of 100 mm Hg. Treatment with dilevalol was less successful in black male patients than in the group at large. There was a tendency for older patients to respond better than younger patients. Prior recent treatment of patients with beta-adrenergic antagonists decreased the effectiveness of the drug. Significant orthostatic hypotension was not noted. Sixty-four patients were transferred to oral dilevalol treatment in combination with a diuretic, and blood pressure in this group averaged 160/100 mm Hg after 1 month of therapy. Dilevalol appears to be a safe and effective drug that can be used intravenously successfully in the majority of patients with severe hypertension and provides an alternative to therapy with other agents. It also is a useful agent for oral treatment of these patients after successful intravenous therapy.

Administration, Oral↗
PubMed1988

Pharmacokinetics and pharmacodynamics of urapidil in severe hypertension.

The clinical response and pharmacokinetics of intravenous urapidil were studied in patients with uncontrolled severe hypertension. Six of nine patients achieved a diastolic blood pressure (DBP) of 100 mm Hg after initial administration of serial bolus doses and were then placed on maintenance infusions. Three of these six patients maintained a DBP 100 mm Hg or lower at infusion rates of 10 to 20 mg/hr, whereas the remaining three patients experienced a loss of DBP control despite rates of 40 mg/hr. Mean DBP was significantly reduced from 126 +/- 6 mm Hg (N = 9) to 105 +/- 15 mm Hg after the bolus phase (N = 9, P less than .05) and 99 +/- 18 mm Hg after the infusion phase (N = 6, P less than .05). Significant reductions in systolic blood pressure were also achieved after bolus and infusion phases. Adverse reactions included drowsiness, tachycardia, nausea and vomiting but were considered mild. Estimated pharmacokinetic parameters included Vz (0.80 +/- 0.20 L/kg), CL (2.53 +/- 0.99 mL/min/kg) and t1/2 (4.0 +/- 1.5 hr). Urapidil safely reduces blood pressure in patients with severe hypertension. An alternative dosing regimen is suggested.

Adolescent↗
PubMed1988

Comparative electrocardiographic and myocardial blood flow effects of rapid atrial pacing and dipyridamole infusion in dogs with chronic coronary artery occlusion.

Altering regional myocardial flow by the use of potent vasodilators as well as increasing oxygen demand by exercise have been employed as diagnostic methods for detecting coronary arterial obstruction. We sought to define the relative capabilities of these two methods to produce abnormal ECG patterns and to alter myocardial blood flow after Ameroid constriction of the left circumflex coronary artery. Atrial pacing to rates of 210 beats/min was performed, followed by intravenous administration of 0.25 and 0.50 mg/kg of dipyridamole. ECGs were recorded to construct body surface isopotential distributions. Flow was measured by serial injections of radiolabelled microspheres. In 15 animals studied after 3 to 5 weeks of Ameroid constriction, pacing increased epicardial flow by 19.14 +/- 7.11% but reduced endocardial flow by 35.69 +/- 12.32%, with a significant reduction (to less than 0.67) in the endocardial/epicardial flow ratio in 12 (80%) dogs; both endocardial and epicardial flows were significantly lower in the ischemic than in the nonischemic bed. Ten dogs developed abnormal ST segment responses of subendocardial ischemia. In contrast, dipyridamole produced a dose-dependent rise in both endocardial (25.33 +/- 8.54% and 55.80 +/- 9.22% after 0.25 and 0.5 mg/kg, respectively) and epicardial (29.13 +/- 7.49% and 66.33 +/- 7.64% after 0.25 and 0.5 mg/kg, respectively) flows without a significant fall in the transmural ratio. These increases were, however, significantly less than those observed in nonischemic bed flow, resulting in a transventricular gradient of blood flow. No dog developed abnormal ECG patterns after dipyridamole infusion. Thus pacing produces both a transmural and a transventricular gradient in blood flow, whereas vasodilation causes only a transventricular flow abnormality.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Effects of residual stenosis on infarct size and regional transmural myocardial blood flow after reperfusion.

This study in dogs was designed to determine the effects of residual stenosis on infarct size and on the transmural distribution of coronary flow in the central and peripheral ischemic perfusion bed. A plastic shunt containing a Doppler flow probe was inserted between the left anterior descending coronary artery and the subclavian artery. The dogs were divided into two groups. Group 1 (N = 7) underwent total shunt occlusion for 2 hours followed by reperfusion at 50% of control flow for 2 hours. Group 2 (N = 8) underwent 2 hours of total occlusion followed by 2 hours of total reperfusion. Regional blood flow was measured by radiolabeled microspheres, and infarct areas were quantitated with triphenyl tetrazolium chloride staining. Infarct sizes expressed as a percentage of the left ventricle or as a percentage of perfusion territory were significantly (p less than 0.05) smaller in animals with total reperfusion (group 2) than in dogs with partial reperfusion (group 1). Endocardial flows in the central infarct zone were significantly higher in dogs with total reperfusion than was observed with partial reperfusion; epicardial flows were not significantly different. In the peripheral region both endocardial flows and epicardial flows with total reperfusion were significantly higher than with partial reperfusion. These studies suggest that residual stenosis after thrombolysis may increase infarct size and reduce endocardial flow in the central infarct zone and transmural flow in the peripheral zone.

Animals↗
PubMed1988

Hemodynamic effects of labetalol in patients with combined hypertension and left ventricular failure.

To investigate the safety of labetalol in the treatment of hypertension in patients with heart failure, sixteen hypertensive patients with a history of congestive heart failure and an ejection fraction at rest less than 45%, had measurements of ejection fraction and cardiac output by first pass radionuclide angiography at baseline, at the end of 2 weeks maintenance with labetalol (titrated to the effective antihypertensive dose of 200-1600 mg daily), and in the post-treatment placebo period. On labetalol, heart rate and blood pressure were significantly lower than placebo at rest and the ejection fraction was higher (30 vs 25%) (p less than 0.05). At maximal exercise on labetalol the heart rate and blood pressure were lower than at placebo maximal exercise (p less than 0.05) and the ejection fraction was higher (32 vs 27%) (p less than 0.01). Exercise tolerance was not changed by labetalol. No patient was discontinued from the study because of worsening heart failure. Dizziness was reported in 5 of 16 patients usually at one visit. Dyspnea that was reported in 4 of 16 patients improved with minor adjustments in digitalis or diuretic dose. In conclusion, labetalol reduces blood pressure in hypertensive patients with left ventricular dysfunction without reducing cardiac performance.

Angiography↗
PubMed1988

The effect of cigarette smoking on the pattern of coronary atherosclerosis. A case-control study.

Cigarette smoking is a risk factor for development of coronary atherosclerosis. We examined the relationship between smoking and the anatomic location of coronary artery stenosis in 8,705 patients undergoing cardiac catheterization for suspected coronary artery disease (CAD). The smoking history of patients with CAD (greater than or equal to 70 percent stenosis) was compared with that of control subjects (0 percent stenosis) for each of nine anatomic locations (proximal, middle, and distal segments of right [RCA], anterior descending [LAD], and circumflex arteries [LCX]), using a case-control method. The odds ratio (OR) estimate of relative risk of CAD for smokers relative to nonsmokers was 2.8, with a 95 percent confidence interval (CI) of 2.5 to 3.1. Relative risk was greater for RCA stenosis (OR = 5.8; CI = 4.6-7.2) than for LCX (OR = 3.5; CI = 2.7-4.5) or LAD (OR = 2.1; CI = 1.8-2.4) lesions when comparing smokers with nonsmokers. After control for age, gender, history of diabetes mellitus, and serum cholesterol level, the adjusted relative risk for an RCA lesion (Mantel-Haenszel odds ratio [MOR] = 4.9) was significantly elevated (p less than 0.05) compared with the LAD (MOR = 1.9) but not with the LCX (MOR = 3.1). The relative risks of CAD were the same (p greater than 0.05) for the proximal, middle, and distal coronary segments. Thus, smoking increased the risk of all coronary lesions but did so more for the RCA than for other vessels, suggesting a spatial pattern to the increased risk produced by smoking.

Adult↗
PubMed1988

Postmenopausal estrogen use and coronary atherosclerosis.

STUDY OBJECTIVE: To determine whether estrogen replacement therapy affects the prevalence of severely obstructive coronary arterial lesions defined by selective coronary arteriography. DESIGN: Case-control study. SETTING: Large, urban, university-affiliated referral hospital. PATIENTS: From a consecutive sample of 6452 women having coronary arteriography between 1972 and 1984, 2188 patients were eligible for study; others were excluded because they were nonmenopausal, had congenital heart defects, valvular heart disorders, primary myocardial disease, or no more than mild to moderate coronary artery disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hospital nurses routinely obtained medication histories. Staff invasive cardiologists interpreted coronary arteriograms. Clinical, laboratory, and angiographic data were abstracted from the cardiac catheterization reports and entered into a computerized registry. Postmenopausal estrogen use for 1444 cases of coronary artery disease (70% stenosis) was compared to that 744 controls (0% stenosis). The odds ratio estimate of the risk of coronary artery disease for estrogen users relative to the risk of coronary artery disease for nonusers was 0.44 (95% confidence interval, 0.29 to 0.67) after adjustment for age, cigarette smoking, diabetes, cholesterol, and hypertension. Postmenopausal estrogen replacement was a significant independent protective factor for coronary artery disease in a multivariate logistic regression model (P = 0.037). CONCLUSION: The data suggest that postmenopausal estrogen treatment reduces the risk for angiographically significant coronary artery disease.

Age Factors↗
PubMed1988

Circulatory congestion in obese hypertensive women: a subset of pulmonary edema in pregnancy.

We describe four obese, chronically hypertensive women presenting with antepartum pulmonary edema in whom invasive hemodynamic monitoring showed elevated wedge pressure, normal to high cardiac index, and normal systemic vascular resistance. Echocardiography revealed large chambers, thick walls, and increased left ventricular mass with normal systolic but abnormal diastolic function. These findings are indicative of intrinsic volume overload occurring in the presence of impaired left ventricular relaxation, a combination resulting in high filling pressures and pulmonary congestion. Diuretic therapy is indicated in this subset of patients, who could not be recognized by the usual clinical parameters such as history and physical examination, chest x-ray, and arterial blood gas.

Adult↗
PubMed1987

Association between the severity of diabetes mellitus and coronary arterial atherosclerosis.

The relation between the severity of diabetes mellitus (DM) and the risk of significant coronary artery lesions were studied in 7,655 patients undergoing coronary arteriography for suspected coronary artery disease (CAD) between 1972 and 1982. The principal treatment regimen for DM was used to estimate the severity of DM. DM treated with insulin was defined as the most severe (n = 244), followed by DM treated with oral agents (n = 344) and with diet only (n = 380); 6,687 patients did not have DM. Severity of DM in patients with CAD (70% or greater diameter stenosis) was compared with that in control subjects without CAD (0% stenosis) for each of 9 anatomic locations (proximal, middle and distal portions of right, anterior descending and circumflex coronary arteries) using a retrospective case-control approach. The risk of CAD was highest in patients with DM treated with insulin (odds ratio estimate of the relative risk [OR = 3.0]), followed by patients with DM treated with oral agents (OR = 1.8) and lastly in those treated with diet alone (OR = 1.4). Severity of DM was a significant (p less than 0.05) independent predictor of CAD in a multivariate logistic regression model, whereas age at onset and duration of DM were not. The relative risk of CAD was the same (p greater than 0.05) for each of the 9 coronary segments. The data suggest that the risk of CAD increases with the severity of DM, which was a stronger predictor of CAD than duration of DM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Prognostic value of the pressure-volume ratio in patients with coronary artery disease.

To determine if the peak-systolic pressure/end-systolic volume ratio [PSP/ESV], a load-insensitive index of left ventricular function, predicted perioperative mortality and long-term survival after coronary artery bypass surgery or medical treatment, 4,829 patients with coronary artery disease were studied retrospectively. Cardiac volumes, ejection fraction, and PSP/ESV ratio were computed using standard methods, and follow-up was performed using annual questionnaires. PSP/ESV ratio values were not significantly different (p = .09) between those who died during hospitalization (n = 101) after coronary surgery and those who were discharged. Long-term follow-up in surgically treated patients demonstrated a 97% 3-year and 93% 5-year survival for those with PSP/ESV over 2.292. These were significantly greater (p = .0026) in value in patients with PSP/ESV less than 1.237 (3-year and 5-year survival of 92 and 79.2%, respectively). In the medical group, survival rate for those with PSP/ESV over 2.292 at 5 years was 89.3%, while for those with PSP/ESV less than 1.237 it was 52.5% (p less than .001). Multivariate analysis, however, showed ejection fraction to be a more significant predictor of survival in both the groups compared with PSP/ESV ratio. Thus, PSP/ESV ratio does predict long-term survival in coronary disease patients treated either surgically or medically. Ejection fraction was nevertheless a more powerful predictor of outcome.

Adult↗
PubMed1987

Alterations in transmural blood flow and body surface ST segment abnormalities produced by ischemia in the circumflex and left anterior descending coronary arterial beds of the dog.

Previous studies have documented a quantitative relation between alterations in transmural myocardial blood flow and body surface electrocardiographic distributions during rapid atrial pacing after chronic occlusion of the left circumflex coronary artery (LCx). Because other studies have described functional differences between the left anterior descending (LAD) and the LCx perfusion beds, we tested the hypothesis that these two territories exhibit quantitative differences in their responses to demand-dependent myocardial ischemia. To do so, 25 sedated dogs were studied 3 weeks after implantation of an ameroid constrictor around the proximal LCx (15 dogs, group I) or the LAD (group II). Oxygen demand was increased by rapid atrial pacing at rates of 90 to 210 beats/min, myocardial blood flow was measured by serial injections of radiolabeled microspheres, and the electrocardiographic consequences were evaluated by isopotential body surface mapping. Endocardial flows and the endocardial/epicardial flow ratio fell to significantly lower levels during atrial pacing in the ischemic LAD bed than in the LCx perfusion zone. Electrocardiographic patterns indicative of subendocardial ischemia also developed with lesser abnormalities in endocardial/epicardial ratios as determined by logistic regression models, in the LAD than in the LCx bed. Thus the LAD bed is more susceptible to ischemia than the LCx region because of differences in collateral blood flow patterns. In addition, the intensity of the surface electrocardiographic potentials during ischemia was significantly greater, as measured by linear regression, after LAD than after LCx obstruction. These data thus demonstrate significant differences between the two cardiac regions as electrocardiographic potential sources during ischemia.

Animals↗
PubMed1987

Diltiazem and propranolol in mild to moderate essential hypertension as monotherapy or with hydrochlorothiazide.

We compared the safety and efficacy of diltiazem and propranolol, and examined demographic factors influencing responses to these agents. One hundred ninety-six patients with supine diastolic blood pressures of 95 to 114 mm Hg were treated with propranolol (80 to 240 mg twice a day) or a sustained-release preparation of diltiazem (60 to 180 mg twice a day) in a double-blind, randomized, parallel group protocol for 6 months. Hydrochlorothiazide was added for patients not achieving the treatment goal. Both agents produced nearly identical and highly significant (p less than 0.001) reductions in supine blood pressure. There were no significant differences at the end of the optional combination therapy phase, although additional reduction with hydrochlorothiazide was slightly greater in the propranolol group. Blood pressure responses in relation to age, gender, race, and smoking history showed that diltiazem produced greater changes in older subjects and women, whereas propranolol was less effective in blacks. However, these differences were not critical.

Adult↗
PubMed1987

Successful aortic valve replacement in osteogenesis imperfecta: with special emphasis on peri-operative management.

Valvular heart disease is a recognized feature of the connective tissue diseases. It occurs to a variable extent in osteogenesis imperfecta and frequently involves the aortic valve. Replacement of the aortic valve, although required, may be complicated by bleeding problems secondary to platelet dysfunction and capillary fragility. A successful aortic valve replacement in a patient with type I osteogenesis imperfecta is described with special reference to hematologic manipulations to control bleeding post-operatively.

Adult↗
PubMed1986

R and S wave changes produced by experimental nontransmural and transmural myocardial infarction.

Electrocardiographic R and S wave changes occur after transmural myocardial infarction. It was the purpose of this study to define the spatial characteristics of these changes and their pathologic determinants after nontransmural as well as transmural necrosis. Twenty-six dogs were studied after occlusion of the left circumflex coronary artery for 60 to 240 minutes, followed by reperfusion. Electrocardiographic potentials were recorded before and 1 week after infarction using an 84 electrode array to compute maximal and root-mean-square R and S wave voltages. Infarct size was quantitated by computer-aided evaluation of heart slices stained by triphenyltetrazolium chloride. R and S wave amplitudes after infarction varied widely from one torso site to another in a pattern generally consistent with the inferoposterior location of the infarcted zones. Although changes in peak R and S wave potentials did not significantly correlate with infarct size, differences in pre- and postocclusion root-mean-square R and S wave amplitudes did, with correlation coefficients of -0.79 and -0.63, respectively. Root-mean-square values increased for small lesions and decreased for larger ones. These data indicate that nontransmural as well as transmural infarction can produce R and S wave changes that are dependent on overall lesion size and the specific lead studied. Such changes may represent useful methods to quantitate lesion size.

Animals↗
PubMed1986

Regional blood flow correlates of ST segment depression in tachycardia-induced myocardial ischemia.

Tachycardia produces subendocardial ischemia and ST segment abnormalities after coronary obstruction. To determine whether a quantitative relationship exists between these ST shifts and transmural blood flow, 19 dogs were studied. Coronary obstruction was produced by ameroid constriction of the left circumflex artery, and tachycardia was generated by atrial pacing at 90 to 210 beats/min. ST shifts were studied by body surface isopotential mapping with an 84-electrode torso grid, and blood flow was quantitated by serial radiolabeled microsphere injections. Isopotential maps at each paced rate, 40 msec into the ST segment, were classified as normal or ischemic based on spatial patterns of voltages. Pacing after 3 weeks of ameroid constriction reduced endocardial/epicardial flow ratios in 11 dogs from 1.16 +/- 0.22 at rest to 0.41 +/- 0.18 at 210 beats/min. Abnormal ST depression developed in these dogs at a rate of 184.0 +/- 16.5 beats/min. Endocardial/epicardial ratios with ST depression (0.45 +/- 0.15) were lower than at those without ST depression (1.05 +/- 0.19; p less than .01). Logistic regression analysis demonstrated that ST depression corresponded to an endocardial/epicardial ratio of 0.67 or less (p less than .01). With this model, 95.5% of data sets were correctly classified. Neither heart rate nor perfusion bed size were significant independent predictors of an ischemic electrocardiographic response. The magnitude of abnormal ST segment shift was significantly correlated (r = .87) with the transmural flow ratio. Thus development of electrocardiographic changes indicative of ischemia corresponds to a predictable degree of flow redistribution and the magnitude of the ST shift is correlated with the intensity of the flow abnormality.

Animals↗
PubMed1985

Natural history of left anterior descending coronary artery obstruction: significance of location of stenoses in medically treated patients.

We examined the prognostic significance of an obstructive lesion in the proximal left anterior descending (LAD) coronary artery. Five-year or longer follow-up data were examined from 311 patients with greater than 70% obstruction of the LAD treated without surgery. Mortality was compared in subsets with lesions proximal to and distal to the first septal perforating artery. Survival curves were worse in patients with proximal than with distal LAD disease (p less than 0.05); lesion location remained a significant determinant of survival when ejection fraction, age, and sex were controlled using a Cox regression model. However, when patient subsets were examined, survival with proximal LAD disease was worse than with distal obstruction only in the presence of an associated right coronary artery lesion and an ejection fraction of less than 40% (p less than 0.01). Patients with proximal LAD plus right coronary lesions had a 5-year mortality rate (34.08 +/- 8.9%) that was not significantly (p greater than 0.05) different from that of a group of 66 patients with greater than 50% narrowing of the left main coronary artery (24.02 +/- 4.3%). Thus, proximal LAD disease is more significant than is a distal lesion only in the presence of right coronary obstruction. This two-vessel combination results in a mortality rate as high as that associated with left main coronary artery obstruction.

Cardiac Catheterization↗
PubMed1985

Effects of experimental myocardial infarction on the ST segment response to tachycardia.

Prior studies have shown that tachycardia results in ST segment depression in dogs with chronic, gradual coronary occlusion. This response was compared with that produced by acute, total occlusion of the left anterior descending artery. Ten dogs served as controls; in another 10 dogs, an ameroid constrictor was implanted about the left anterior descending artery. This artery was acutely ligated in a third set of 10 animals, and in a final set of 10, the distal left anterior descending coronary vasculature was embolized by latex injection. Tachycardia was produced by atrial pacing from rates of 90 to 250 beats/min using implanted atrial electrodes. Electrocardiographic signals registered from 84 torso electrodes were used to construct body surface isopotential maps during the ST segment. In normal dogs, pacing increased repolarization potentials without shifts in spatial features. New and abnormal anterior negativity, correlating with significant ST depression, appeared at rates of 170 beats/min or faster in dogs with ameroid constriction. However, in both groups with acute occlusion that produced transmural myocardial infarction, tachycardia resulted in increases in anterior ST elevation and reciprocal ST depression. Specific findings demonstrated the lead dependency of the response to tachycardia and the greater than normal increase in potential magnitudes after infarction than in control cases. The similarity of the response with acute occlusion and with embolization suggested that the response to tachycardia after infarction was not dependent on coronary collateral function but may represent a direct electrophysiologic effect of rate. Thus, these acute occlusion models simulate exercise-induced ST segment elevation as it may be seen clinically.

Animals↗