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Biomedical subjects

R Kloner

Publications and source records attributed to R Kloner.

10 recordsLinked to original sources
PubMed2006

Erectile dysfunction and hypertension.

Recent analyses suggest that about 67-68% of men with hypertension have some degree of erectile dysfunction (ED). With about 25 million men in the US with hypertension, substantial numbers of hypertension-related ED exist that tend to be of a more severe nature than the general population. Men with ED are also more likely to have hypertension. Thiazide diuretic and beta-blocker therapy may contribute to ED. Phosphodiesterase-5 (PDE5) inhibitors are effective therapy in men with ED owing to hypertension who are taking antihypertensive medicines including those on multiple antihypertensive medicines. The addition of PDE5 inhibitors to usual common antihypertensive medicines (diuretics, beta blockers, calcium blockers, angiotensin converting enzyme inhibitors and angiotensin receptor blockers) results in either no or small additive reductions in blood pressure (BP) and no increase in serious clinical adverse events. There are however precautions regarding the use of PDE5 inhibitors in patients taking alpha blockers for either hypertension or benign prostatic hypertrophy, as some patients may develop orthostatic hypotension. Organic nitrates remain an absolute contraindication for PDE5 inhibitors because synergistic and symptomatic reductions in BP may occur in some patients with this drug combination.

Antihypertensive Agents↗
PubMed1990

The effect of balloon angioplasty on vasa vasorum blood flow in canine coronary arteries.

To assess the effects of balloon dilatation on vasa vasorum flow, we performed percutaneous transluminal coronary angioplasty on the circumflex arteries of 12 dogs. Left anterior descending and circumflex coronary vasa vasorum flows were measured with radioactive microspheres at baseline, during, and 10 minutes after a 3-minute, 8 atm balloon inflation. With inflation, vasa vasorum flow at the balloon dilatation site profoundly decreased (from 0.25 +/- 0.08 to 0.03 +/- 0.01 ml/min/gm). The flow returned to normal within 10 minutes after deflation. This effect was not mediated by hemodynamic deterioration during coronary occlusion and did not occur in the contralateral coronary artery. Endomyocardial flow in the distribution of the dilated artery decreased markedly during balloon inflation (from 1.14 +/- 1.9 to 0.08 +/- 0.04 ml/min/gm), which confirmed coronary occlusion. We conclude that a prolonged decrease in vasa vasorum flow is not produced by experimental balloon angioplasty, which makes it unlikely that a sustained vasa vasorum flow reduction plays a role in the maintenance of patency or the induction of restenosis.

Angioplasty, Balloon↗
PubMed1989

The clinical syndrome of 5-fluorouracil cardiotoxicity.

5-fluorouracil (FUra) is one of the most frequently used drugs in cancer treatment, particularly in combination with other agents. Its activity when administered as an infusion rather than a bolus has led to a renewed and increased use. A cardiotoxicity that mimics ischemia has been associated with the administration of FUra in cancer patients. This cardiotoxicity may manifest itself as: (a) dysrythmias with and without cardiorespiratory symptoms (b) ECG changes with and without cardiorespiratory symptoms (c) cardiorespiratory symptoms with and without ECG changes (d) acute myocardial infarct; symptoms and ECG changes (e) ventricular dysfunction (f) cardiogenic shock and (g) sudden death. Several case studies which illustrate the cardiotoxic sequelae that may be associated with the use of this drug are discussed. The incidence, contributing factors, risk factors and mechanisms underlying this phenomenon are undetermined. No appropriate recommendations for monitoring patients or for predicting those patients that will develop such toxicity while receiving FUra can be made at present. Prospective studies to determine the true incidence, spectrum and mechanisms causing this syndrome are ongoing and required for its understanding and prevention.

Adult↗
PubMed1988

Effect of indomethacin in the late phase of coxsackievirus myocarditis in a murine model.

Previous studies have shown that indomethacin administered during the early phase of experimental myocarditis may exacerbate the disease process. It is unknown whether late administration of this agent is safe. Therefore, the effect of indomethacin administration during the late phase of coxsackievirus B3 murine myocarditis was investigated. Forty 3-week-old CD1 mice each received a 3 x 10(4) median tissue culture-infective dose of coxsackievirus intraperitoneally. On day 10 of infection, mice were randomized to receive either indomethacin or normal saline solution for 10 days, and 10 mice from each group were killed on days 20 and 30 of infection. Heart weight and size and serum atrial natriuretic peptide were similar in both groups on days 20 and 30. On day 20, pathologic scores for the degree of inflammation and necrosis were 1.7 and 1.0 for the indomethacin group versus 1.4 and 1.7 for the saline solution group. On day 30, pathologic scores were 0.3 and 0.6 for the indomethacin group versus 0.5 and 0.6 for the saline solution group. In addition, mineralization was absent in indomethacin-treated animals on day 20 after infection, but it was present in half of the control animals at that time. The degree of mineralization did not differ on day 30 between the two groups. These findings suggest that indomethacin given in the late phase of coxsackievirus myocarditis has no deleterious effects at 30 days.

Animals↗
PubMed1985

Contrast echocardiographic estimation of regional myocardial blood flow after acute coronary occlusion.

Contrast echocardiography can predict pathologic area at risk during acute coronary occlusion. In this study we evaluated (1) whether the intensity and timing of contrast appearance in ischemic regions can provide a quantitative measure of residual myocardial perfusion, and (2) whether changes in these parameters observed after serial injections reflect changes in blood flow to acutely ischemic tissue. Supra-aortic hydrogen peroxide contrast echocardiography was performed in 12 consecutive dogs at 1, 20, and 120 min after acute circumflex coronary occlusion. Contrast enhancement was determined qualitatively with a segmental four-point scoring system based on the appearance time and peak perceived intensity of contrast enhancement and quantitatively with a computer algorithm designed to reflect these parameters. Comparison was made in each segment to concomitant radioactive microsphere blood flow. Qualitative scoring related systematically to normalized segmental blood flow (3+ = 93%; 2+ = 61%; 1+ = 32%; 0 = 18%; p less than .01 for each vs adjacent value), as did quantitative analysis including all segments (r = .78; p less than .01) and isolated to the ischemic region (flow = 1.13 intensity change +6.8%; r = .83, p less than .001). Changes in microsphere flow in ischemic regions between sequential observations were correlated with changes in qualitative score (r = .88, p less than .001) and results of quantitative analysis (r = 0.70, p less than .01). The amount of contrast enhancement can provide quantitative information about residual myocardial blood flow in ischemic regions and can also be used to track changing patterns of flow in vivo after acute coronary occlusion.

Animals↗
PubMed1982

Limitation of myocardial infarct size after surgical reperfusion for acute coronary occlusion.

We investigated the effect of different forms of myocardial protection on infarct size and on the necrotic myocardial process after reperfusion for acute occlusion of the left anterior descending coronary artery (LAD) in dogs. Three control groups were formed: a 1 hour, 2 hour, and 6 hour locally ischemic control. Three experimental groups were locally ischemic for 1 hour and then reperfused after an additional hour of local ischemia on cardiopulmonary bypass with the heart protected by intermittent ischemia, cold potassium cardioplegia, or blood cardioplegia. To delineate the area at risk, the LAD was temporarily occluded 30 seconds before the 6 hour sacrifice time, and monastral blue dye was injected through a polyvinyl catheter placed in the left atrial appendage. The LAD area at risk (AR) was not stained. After 6 hours the heart was excised and treated with triphenyltetrazolium chloride (TTC) to define the area of myocardial necrosis (AN). The AN/AR ratio was determined for each animal by planimetry. Mean values were then computed in each of the six groups and evaluated by the Student's t test for paired data. The 1 hour control group had an AN/AR ratio of 64% +/- 5%; the 2 hour control group, 80% +/- 6%; and the 6 hour control group, 92% +/- 1%. The intermittent ischemia group had an AN/AR ratio of 83% +/- 2%; the crystalloid cardioplegic group (2 hours of ischemia) had a ratio of 69% +/- 4%, similar to the 1 hour control but significantly smaller than the 2 hour control (p less than 0.05); and the blood cardioplegia group had an AN/AR ratio of 48% +/- 8%, significantly better than any other group. These data demonstrate that myocardial necrosis after coronary occlusion is a time-related phenomenon and will increase to encompass a large fraction of the area at risk unless there is physical or pharmacologic modification during reperfusion, such as crystalloid or blood cardioplegia.

Animals↗
PubMed1978

Cellular electrophysiological marker of irreversible ischemic myocardial injury.

Glass microelectrode studies on posterior papillary muscle (PPM) slice preparations from 20 pentobarbital-anesthetized dogs (15 subjected to prior circumflex coronary artery ligation, 5 to sham ligation) have resulted in the definition of an electrophysiological marker of irreversible ischemic injury, namely, findings of areas composed of cells unable to generate a significant resting potential (less than -25) mV), designated "electrically inactive areas." Electrically inactive areas were essentially confined to PPM from dogs with circumflex coronary ligation; the incidence and distribution of the areas was related to duration of ischemia. Correlative phase- and light-microscopic studies demonstrated close correspondence between such areas and morphological evidence of irreversible ischemic injury. Analysis of frequency and distribution of electrically inactive areas permits quantitative assessment of the extent and spatial distribution of irreversible injury. This method has been used to quantitate injury in PPM from dogs that had been subjected to ligation for varying time periods. The potential utility of this method for evaluation of interventions designed to protect against ischemic injury and to assess electrical properties of surviving cells is considered.

Animals↗
PubMed1976

The prevalence of tuberculosis and positive tuberculin skin tests in a steroid-treated asthmatic population.

The prevalence of active tuberculosis and positive tuberculin skin tests was assessed in 132 corticosteroid-treated asthmatics for an evaluation period that represented 620 corticosteroid-years of therapy. There was no evidence of active tuberculosis in any of these patients. Positive intermediate-strength tuberculin tests were present in 28% of patients and correlated with increased age. In patients treated with daily corticosteroids, tuberculin negativity was associated with a higher dose of corticosteroids. Positive second-strength tuberculin tests were found in 42.3% of the patients with negative intermediate-strength tests and also correlated with increased age. Based on these data as well as the prevalence of significant liver disease in older patients receiving isoniazid (INH), routine INH chemoprophylaxis for corticosteroid-treated asthmatic patients, regardless of their tuberculin cutaneous reactivity, is not indicated.

Adolescent↗
PubMedDate not supplied

Erectile dysfunction in patients with coronary artery disease.

Recent studies suggest that erectile dysfunction (ED) may be an early marker of endothelial dysfunction and coronary artery disease (CAD). Conversely, patients with CAD commonly have ED. The phosphodiesterase 5 (PDE5) inhibitors are very effective for the treatment of ED in patients with CAD. Numerous studies show that this class of drugs is in general safe in patients with stable CAD and these agents do not exacerbate ischemia in men with CAD undergoing exercise stress testing. Analysis of placebo-controlled trials did not show an increase in cardiovascular events among men receiving PDE5 inhibitors, and post-marketing surveillance studies with sildenafil did not observe an increase in cardiovascular events compared to expected age-matched rates. Organic nitrates remain a contraindication for PDE5 inhibitors and alpha blockers have precautions/contraindications depending upon specific drugs. The Princeton Consensus Guidelines (soon to be updated) suggest a logical approach to the patient with CAD seeking therapy for sexual dysfunction.

3',5'-Cyclic-GMP Phosphodiesterases↗