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Biomedical subjects

J L Mehta

Publications and source records attributed to J L Mehta.

At least 235 records · Page 13Linked to original sources
PubMed1985

Influence of calcium-channel blockers on platelet function and arachidonic acid metabolism.

Available data indicate that platelet function and arachidonic acid metabolism are important factors in hemostasis and regulation of vascular tone. Plasma membrane and intracellular mobilization of calcium ions are intimately related to platelet activation and release of platelet contents. Release of arachidonic acid from membrane phospholipids as well as subsequent synthesis and release of vasoconstrictor thromboxane A2 are also regulated by movement of calcium ions. Adenosine 3':5'-cyclic phosphate in turn controls levels of free calcium ions in platelets and regulates calcium-dependent reactions. Slow-channel calcium blockers, such as verapamil, diltiazem and nifedipine, inhibit platelet activation in vitro, and decrease platelet adhesion intravascularly. These agents have also been shown to decrease platelet nucleotide release and thromboxane A2 generation. Some preliminary data suggest that calcium blockers also increase generation of vasodilator and platelet antiaggregant prostacyclin, which could contribute to decrease in platelet function. These effects of calcium blockers on platelet function and arachidonic acid metabolism could contribute in part to their efficacy in patients with ischemic heart disease.

Animals↗
PubMed1985

Improvement in exercise performance with nisoldipine, a new second-generation calcium blocker, in stable angina patients.

Safety and efficacy of a new dihydropyridine calcium antagonist, nisoldipine, were studied in 15 patients with proved coronary artery disease and positive exercise treadmill tests. After withdrawal of current therapy and a 2-week placebo phase, patients were given nisoldipine 10, 20, and 40 mg daily (divided into two daily doses), each dose for a 2-week period. Exercise treadmill testing was performed twice during the placebo and once at the end of each nisoldipine phase. Maximal duration of exercise increased with all doses of nisoldipine. Time to 1 mm ST segment depression also increased with all doses of nisoldipine. Peak time to angina was similarly prolonged. Peak exercise double product (heart rate X systolic blood pressure) was unaffected by all doses of nisoldipine. Angina frequency and nitroglycerin consumption decreased during nisoldipine therapy in all patients. Side effects from therapy were only minor. Twice daily therapy compared to three to four times daily therapy with other calcium blockers is an advantage of nisoldipine.

Adult↗
PubMed1985

Long-term experience with lofexidine in the treatment of mild-to-moderate essential hypertension.

This study describes sustained efficacy and safety of lofexidine in hypertensive patients. Twenty-one male patients (mean age 55 +/- 9 yr) who had previously completed a short-term trial of lofexidine entered this open-label trial. The daily dose of lofexidine was titrated over three months to a maximum of 1.6 mg or an erect diastolic blood pressure less than 90 mm Hg. Hydrochlorothiazide was added when necessary. Thereafter, each patient was evaluated for blood pressure (BP) response, compliance, side effects, hepatic, renal, or hematological abnormalities every three months for two years. Sustained BP reduction with lofexidine was achieved but not without concomitant diuretic therapy. There were no clinically important changes in heart rate or hepatic, renal, or hematological profiles. Side effects were frequent but severe enough to warrant discontinuation in only four patients. The side-effect profile was similar to that of clonidine. We recommend concurrent diuretic use to maximize effectiveness of lofexidine.

Adolescent↗
PubMed1984

Comparative efficacy and safety of lofexidine and clonidine in mild to moderately severe systemic hypertension.

The comparative efficacy and safety of lofexidine and clonidine in patients with mild to moderate systemic hypertension were evaluated. Patients who met established criteria were administered lofexidine or clonidine in a double-blind manner. The dose of either drug, along with hydrochlorothiazide if necessary, was titrated to blood pressure response or to the occurrence of side effects. Treatment with the dose established during titration was continued for 12 weeks. Blood pressure and the occurrence of side effects were evaluated during weekly clinic visits. Twenty-six patients completed all portions of the study. The decrease in blood pressure compared with that with the placebo was significant for both drugs (p less than 0.05). The daily dose of clonidine required for blood pressure control was less than that of lofexidine (p less than 0.05). Concomitant diuretic therapy was required equally as often for both drugs. Clonidine caused adverse effects more frequently than did lofexidine. The effectiveness of lofexidine is comparable to that of clonidine, but lofexidine has a lower incidence of toxicity.

Adolescent↗
PubMed1984

Platelet function and biosynthesis of prostacyclin and thromboxane A2 in whole blood after aspirin administration in human subjects.

Small doses of aspirin have been shown to inhibit platelet thromboxane A2 while sparing vascular prostacyclin synthesis. Because leukocytes generate prostacyclin and participate in thrombosis along with platelets, the effects of three different doses of aspirin (40, 325 and 650 mg) on platelet function as well as on endogenous biosynthesis of thromboxane A2 and prostacyclin in whole blood were examined. In normal volunteers given a single 40 mg dose of aspirin, platelet aggregation and adenosine triphosphate release were inhibited for 24 hours. In contrast, platelet function was inhibited for 4 to 7 days in volunteers given 325 or 650 mg of aspirin. Platelet and whole blood generation of thromboxane A2 was inhibited less than 60% by the 40 mg dose, but almost completely by both the 325 and 650 mg doses. Likewise, whole blood generation of prostacyclin was inhibited 70% by the 40 mg dose and over 90% by the larger doses. Inhibition of thromboxane A2 as well as of prostacyclin was evident for 4 days with the 40 mg dose and for 7 days with the larger doses. Decreases in whole blood thromboxane A2 and prostacyclin with any dose of aspirin were of similar magnitude. These data indicate that aspirin in doses of 40 to 650 mg inhibits platelet function and biosynthesis of thromboxane A2 and prostacyclin in whole blood in human beings in a dose-dependent fashion.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Effects of nitrendipine and hydralazine on plasma catecholamines in essential hypertension.

We compared the efficacy and safety of nitrendipine with that of hydralazine in 21 subjects with essential hypertension. Nitrendipine or hydralazine was given in a double-blind manner after a placebo period. Dose was titrated to diastolic blood pressure (BP) less than or equal to 90 mm Hg and the dose established during titration was continued for 5 to 7 wk. Both supine and erect BP were decreased by both drugs, but heart rate was affected only minimally. Myocardial oxygen demand decreased only with nitrendipine (P less than 0.05), although the change may have been the result of somewhat higher systolic BP while on placebo. Hydralazine induced minimal changes in levels of plasma catecholamines, but plasma norepinephrine levels rose in subjects on nitrendipine. Side effects encountered with both drugs were much the same, although nitrendipine was more often associated with mild fatigue. There were mild elevations in liver function parameters in two subjects on nitrendipine. There was little difference between the effects of nitrendipine and hydralazine in hypertension.

Adult↗
PubMed1984

Efficacy and safety comparison of nitrendipine and hydralazine as antihypertensive monotherapy.

One-hundred and five patients with hypertension received nitrendipine (10-40 mg/day) or hydralazine (50-200 mg/day) in a double-blind randomized design. Nitrendipine decreased supine blood pressure 15/10 mm Hg, and hydralazine decreased it 11/11 mm Hg. Standing blood pressure was decreased 15/12 mm Hg by nitrendipine and 12/11 mm Hg by hydralazine. Supine and standing heart rate rose significantly after both drugs. Blood pressure variation through one dosing interval increased 42% when hydralazine was given but was not altered by nitrendipine. Side-effects from the two drugs were similar in patients who completed the study, but six patients discontinued participation due to side-effects of hydralazine, while only one discontinued due to nitrendipine side-effects. Ten patients required propranolol for hydralazine side-effects, and only three required it for nitrendipine side-effects. Nitrendipine and hydralazine are equally effective as antihypertensive monotherapy in patients with mild to moderate hypertension for periods up to 7 weeks, but nitrendipine appears to be better tolerated.

Adult↗
PubMed1984

Biochemical and ultrastructural integrity of the saphenous vein conduit during coronary artery bypass grafting. Preliminary results of the effect of papaverine.

Factors associated with early and late graft patency related to aorta-coronary artery bypass grafting with a reversed segment of saphenous vein are clinically important. The present investigation examines the biochemical and electron microscopic integrity of this venous conduit intraoperatively with regard to pharmacologic manipulation with papaverine. Portions of saphenous vein were analyzed in 22 patients undergoing coronary artery bypass operations. Levels of a stable derivative of prostacyclin, 6-keto-PGF1 alpha, were measured by radioimmunoassay. Scanning as well as transmission electron microscopy was also performed. In particular, the efficacy of local vein treatment with papaverine, a phosphodiesterase inhibitor, was evaluated. We found that levels of 6-keto-PGF1 alpha in venous effluent showed a biphasic response with initial elevation followed by a relative depression after papaverine exposure. There were no such changes observed in veins subjected to a balanced electrolyte solution (Plasma-Lyte). In addition, levels of the platelet-inhibitory substance 6-keto-PGF1 alpha in venous tissue were less in papaverine-treated veins than those found in veins treated only with the balanced electrolyte solution (Plasma-Lyte). Furthermore, evidence for ultrastructural damage was also somewhat greater in the papaverine-treated group. An alternative method of dilating the saphenous vein after harvesting, which involves the creation of the proximal aorta-coronary anastomosis first and gentle finger manipulation subsequently, appeared to minimize venous injury. Under present clinical conditions, it appears that some amount of injury is inevitable during harvesting and suturing of the human saphenous vein during coronary bypass grafting.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Titrates for treatment of unstable angina pectoris and coronary vasospasm.

The treatment of a patient with unstable angina at the time of the initial presentation of the physician can begin with nitrates. The beneficial action of nitrates are several. Nitrates dilate epicardial coronary arteries as well as many coronary artery stenoses. They may be effective because of this action plus a marked effect on decreasing ventricular volume and ventricular end diastolic pressure. Perhaps the best way to manage patients with severe angina that may be in part related to coronary artery vasoconstriction is to combine a long-acting nitrate with a calcium antagonist. The combined use of nitrates and calcium antagonists will (1) dilate the coronary arteries to maintain coronary blood flow, (2) decrease systemic arterial pressure and thus decrease peripheral vascular resistance, and (3) dilate peripheral veins and thus decrease ventricular volume and pressure. When proper doses are used, the combination may be more effective than either drug alone. Of course, proper dosing must be determined for the individual patient by the physician. Initial treatment with the nitrates should begin with small doses and gradually build up. Similar dosing schedules should be used for the calcium antagonists. Both doses can be increased to high levels is the clinical situation warrants it.

Adrenergic beta-Antagonists↗
PubMed1982

Optimal lidocaine dosing in patients with myocardial infarction.

A decrease in hepatic clearance and volume of distribution in patients with congestive heart failure frequently leads to toxicity when drugs such as lidocaine are administered. To determine the effect of adjusted dosing of lidocaine in patients with myocardial infarction, we studied 32 patients receiving lidocaine either by a conventional method (control group: 1-2 mg/kg bolus, then 1 to 4 mg/min) or by an adjusted regimen based on the presence or absence of heart failure [experimental group: 1-2 mg/kg bolus; then, class I (no heart failure), 35 to 88 micrograms/kg/min; class II (heart failure), 12 to 35 micrograms/kg/min]. Plasma lidocaine levels were determined at 2 and 5 h of the infusion by enzyme multiplied immunoassay technique (EMIT) and gas liquid chromatography (GLC). Ten of 33 determinations in the control group were in the toxic range, i.e., greater than 6 micrograms/ml, and four others were subtherapeutic, i.e., less than 2 micrograms/ml. In contrast, 13 of 16 determinations in the experimental group were in the therapeutic range, and none were in the toxic range. These data show that administration of lidocaine by a conventional method may produce diverse plasma levels that may occasionally be in the toxic range. Modified dosing based on cardiac status may result in optimal levels in most patients.

Adult↗
PubMedDate not supplied

Antioxidants and vitamins in your cardiac patient: are they helpful?

There is an intense interest in the use of antioxidants in the prevention and treatment of coronary artery disease (CAD). Oxidants or free radicals are necessary for human physiology, but excess of free radical formation and release can lead to vascular injury and lipid peroxidation. Some, but not all, studies show beneficial effect of exogenous antioxidants, primarily vitamin E, in patients with CAD. This article summarizes our current understanding of free radicals and their role in physiology and the role of antioxidants in disease prevention with special emphasis on the potential adverse effect of treatment of patients with large doses of antioxidants.

Antioxidants↗
PubMedDate not supplied

Laser endarterectomy: a comparison of thrombotic potential following CO2 laser vs surgical endarterectomy.

Although laser endarterectomy has recently been suggested as useful in the treatment of arteriosclerotic obstructions, the "in vivo" clotting effects have not been well delineated. In this study, the common carotid and femoral arteries of ten mongrel dogs were exposed, and alternating 1 cm segments of each artery were treated with surgical endarterectomy and low-powered CO2 laser endarterectomy. Segments were then harvested, and subjected to histologic examination and vascular prostacyclin synthesis determinations, as measured by 6-keto PFG1a radioimmunoassay. Gross examination and light and scanning electron microscopy showed increased platelet aggregation and more extensive damaging of the underlying media of the laser compared to the surgical segments. Six-keto PFG1a levels were significantly lower (p = 0.001) in the laser compared to surgical sites (mean 232 +/- 72 pg/mg vs 515 +/- 144 pg/mg), or controls (895 +/- 337 pg/mg). These findings suggest that laser endothelial evaporation leads to increased thrombotic potential in the early post-operative period in comparison to surgical endarterectomy.

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

Plasma lipid profiles and antihypertensive agents: effects of lisinopril, enalapril, nitrendipine, hydralazine, and hydrochlorothiazide.

Previous studies have documented potentially adverse effects of diuretics and beta-blocking agents on plasma lipid profiles. This study was designed to establish the effects on lipid profiles of the angiotensin-converting enzyme inhibitors lisinopril and enalapril, alone and in combination with hydrochlorothiazide (HCTZ), the calcium-channel blocker nitrendipine, HCTZ, and hydralazine. After a two-week, single-blind, placebo phase, 77 patients with essential hypertension were given active agent as monotherapy in a double-blind fashion for 8-20 weeks. The dose of each agent was titrated to achieve diastolic blood pressure less than 90 mm Hg. At the end of placebo and treatment phases, plasma was analyzed for triglycerides, total cholesterol, and high-(HDL), and low-density lipoprotein (LDL) cholesterol. Overall, few changes in lipid contents were noted. Total cholesterol decreased during therapy with hydralazine but increased in patients receiving the combination of lisinopril and HCTZ. HDL cholesterol was depressed in those taking HCTZ alone and in combination with lisinopril. LDL cholesterol was lowered during therapy with hydralazine but was otherwise unaffected by all other agents. None of the agents evaluated significantly affected triglyceride concentrations. Thus, monotherapy with lisinopril, enalapril, and nitrendipine do not affect plasma lipid concentrations. Hydralazine lowers total and LDL cholesterol. If these findings are confirmed in trials with larger numbers of patients, these effects on lipid profiles may influence choice of agent in the therapy of essential hypertension.

Adult↗