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Biomedical subjects

D D Waters

Publications and source records attributed to D D Waters.

At least 55 records · Page 3Linked to original sources
PubMed1996

Functional and structural alterations with 24-hour myocardial hibernation and recovery after reperfusion. A pig model of myocardial hibernation.

BACKGROUND: Short-term myocardial hibernation of 3 hours resulting from a moderate resting coronary flow reduction has been reproduced in pigs. This study was designed to determine whether any structural changes accompany short-term hibernation caused by a moderate flow reduction maintained for 24 hours and whether any such structural alterations are reversible after reperfusion. METHODS AND RESULTS: A severe left anterior descending coronary artery (LAD) stenosis was created with a reduction of resting flow to approximately 60% of baseline and maintained for 24 hours. Regional coronary flow was measured by a flowmeter; wall thickening was determined by echocardiography, and local metabolic changes were measured. Of 17 pigs, 11 completed the study protocol of 24 hours. The LAD flow was reduced from 0.91 +/- 0.11 to 0.52 +/- 0.13 mL.min-1.g-1, a 43% mean decrease, at 15 minutes after the LAD stenosis and was maintained at 0.56 +/- 0.11 mL.min-1.g-1 at 24 hours. The reduction of regional coronary flow initially produced acute myocardial ischemia, as evidenced by reduced regional wall thickening (from 37.2 +/- 6.9% at baseline to 11.5 +/- 6.8%), regional lactate production (-0.34 +/- 0.28 mumol.g-1.min-1), and a decrease in regional coronary venous pH (from 7.41 +/- 0.035 at baseline to 7.30 +/- 0.030). At 24 hours, the reductions in coronary flow and wall thickening were maintained relatively constant and the rate-pressure product was relatively unchanged, but lactate production ceased and regional H+ concentration normalized, with a tendency toward a further reduction in regional oxygen consumption, from 3.10 +/- 0.90 mL.min-1.100 g-1 at 15 minutes after stenosis to 2.52 +/- 0.95 mL.min-1.100 g-1 at 24 hours (P = .06), indicating metabolic adaptation of the hypoperfused regions. Of 11 pigs, 6 were free of myocardial infarction; 3 had patchy necrosis involving 4%, 5%, and 6% of the area at risk; and 2 other pigs had a few scattered myocytes with necrosis, detected only by light and electron microscopy. Ultrastructural changes consisted of a partial loss of myofibrils and an increase in mitochondria and glycogen deposition. Regional wall thickening recovered 1 week after reperfusion in most pigs, and the ultrastructural changes reverted to normal. CONCLUSIONS: In this pig model, moderately ischemic myocardium undergoes metabolic and structural adaptations but preserves the capacity to recover both functionally and ultrastructurally after reperfusion.

Actin Cytoskeleton↗
PubMed1996

Factors associated with the release of cardiac troponin T following percutaneous transluminal coronary angioplasty.

BACKGROUND: Recent studies have suggested that immunoassay of cardiac troponin T (cTnT) provides a more sensitive measurement of myocardial necrosis than creatine kinase MB (CK-MB) mass concentration. HYPOTHESIS: The purpose of this study was to compare the release of cTnT and CK-MB isoenzyme in patients undergoing percutaneous coronary angioplasty, and to investigate the clinical, procedural, and angiographic correlates of abnormal elevations of both of these markers. METHODS: Total creatine kinase (total CK), CK-MB, and cTnT levels were measured immediately before and 12 h following intervention in 110 patients, including 100 consecutive patients undergoing coronary angioplasty and 10 control patients undergoing diagnostic cardiac catheterization. All patients had normal levels of all three markers at baseline. A postintervention total CK level > 225 U/l, an increase in CK-MB > 5.0 ng/ml, and/or an increase in cTnT > 0.04 ng/ml were considered indicative of myocardial injury. RESULTS: Coronary angioplasty was successfully performed in all 100 patients without emergency bypass surgery or death, although six patients required emergent placement of an intracoronary stent for threatened closure. Eight patients demonstrated an abnormal increase in total CK, including six who were undergoing primary angioplasty for an acute myocardial infarction. One of these patients sustained a Q-wave infarction. Post angioplasty, 18 patients had elevations of both CK-MB and cTnT, 23 had elevations of only cTnT, and the remaining 59 patients had elevations of neither. All patients with CK-MB elevation also had cTnT elevation. Neither serologic marker increased in the diagnostic catheterization control patients. In comparison with patients without postintervention cTnT rise, patients with abnormal cTnT levels had a higher incidence of complex lesion morphology (p < 0.01) and intracoronary thrombus (p < or = 0.0001) prior to coronary angioplasty, and a higher incidence of coronary dissection (p < or = 0.01), abrupt closure (p < or = 0.05), and side-branch occlusion (p < or = 0.01) during angioplasty. In patients with elevation of both cTnT and CK-MB, postintervention CK-MB levels were 12-fold higher and cTnT levels were 21-fold higher than in patients with isolated elevation of only cTnT (p < 0.01). CONCLUSIONS: These data indicate that > 40% of patients undergoing coronary angioplasty have evidence of minor degrees of myocardial damage, as evidenced by cTnT release. High-risk coronary lesions and both minor and major complications of angioplasty are associated with cTnT release. cTnT appears to be a more sensitive marker of myocardial injury than CK-MB under these circumstances. In comparison with isolated cTnT rise, elevation of both CK-MB and cTnT may be indicative of greater levels of myocardial injury.

Aged↗
PubMed1996

Pathophysiology and initial management of the acute coronary syndromes.

Acute coronary syndromes are responsible for more than half a million hospital admissions each year in the United States alone. Plaque rupture is the precipitating pathophysiologic event. The degree of narrowing of plaques that rupture is not necessarily severe, in the range of 30% to 70% diameter stenosis. Plaques containing large lipid pools with only thin fibrous caps are most at risk. The site of rupture is most often at the shoulder of the plaque, where stress is highest. Clusters of macrophages are often seen at these points. Most plaque ruptures heal without causing symptoms, perhaps leaving a narrowing somewhat more severe than before. Plaque ruptures that expose larger areas of thrombogenic intramural debris to flowing blood in areas of high turbulence are most likely to provoke more extensive thrombosis. Risk factors, particularly smoking and hypercholesterolemia, cause increased thrombin deposition at the site of deep arterial injury. Thrombin deposition causes local coronary vasoconstriction that may contribute to the development of ischemia. Whether plaque rupture with thrombosis causes infarction, unstable angina, or no symptoms at all depends on the site of the lesion, its severity, and whether the jeopardized myocardium is served by collaterals. Aspirin, heparin, and, potentially, the newer agents provide benefit in each of the acute coronary syndromes.

Angina, Unstable↗
PubMed1995

Enhanced intracoronary thrombolysis with urokinase using a novel, local drug delivery system. In vitro, in vivo, and clinical studies.

BACKGROUND: Current pharmacological regimens for treating intracoronary thrombus in the cardiac catheterization laboratory generally involve the administration of thrombolytic agents that result in a systemic fibrinolytic state and/or require prolonged arterial drug infusion. The purpose of the present study was to assess a new technique for treating intracoronary thrombus consisting of the local infusion of limited quantities of urokinase with a novel drug delivery device. METHODS AND RESULTS: THe Dispatch coronary infusion catheter is a new local drug delivery system that allows for the prolonged infusion of therapeutic agents at an angioplasty site while distal coronary flow is maintained. Three experimental protocols were performed to determine the in vitro, in vivo, and clinical efficacy of this device. First, in vitro thrombolysis of fresh, porcine thrombus trapped in a 4-mm plastic tube with a 50% constriction and perfused with 20% porcine plasma was measured. Twenty-three thrombi were weighed before and after no treatment (n = 5), "systemic" urokinase administration (n = 4), local infusion of 150,000 U urokinase with a standard end-hole catheter (n = 4), local infusion of saline with the Dispatch catheter (n = 5), and local infusion of 150,000 U urokinase with the Dispatch catheter (n = 5). Second, 25 porcine coronary arteries in 23 pigs were dilated in vivo with conventional balloon angioplasty and then treated with 123I-labeled urokinase that was administered either by the Dispatch catheter (150,000 U; n = 16), intravenous systemic bolus (1,000,000 U; n = 3), guiding catheter infusion (500,000 U; n = 3), or local end-hole catheter infusion (150,000 U; n = 3). All vessels were subsequently harvested to quantify intramural deposition and subsequent washout of urokinase at the angioplasty site. Finally, 19 patients with angiographic evidence of intracoronary thrombus were treated with local urokinase infusion with the Dispatch catheter either before or after balloon angioplasty or directional atherectomy. In vitro studies demonstrated that infusion of urokinase with the Dispatch catheter decreased thrombus weight by 66% compared with no treatment (-25%), "systemic" urokinase administration (25%), end-hole catheter urokinase infusion (32%), or infusion of saline by the Dispatch catheter (32%) (P < or = .005). In vivo studies demonstrated immediate deposition of 0.12% of the urokinase delivered by the Dispatch catheter to the angioplasty site, compared with 0.0007% with systemic bolus, 0.003% with guiding catheter infusion, and 0.007% with local infusion with an end-hole catheter (P < .001). Urokinase deposited by the Dispatch catheter persisted intramurally for at least 5 hours. Patient studies demonstrated reduction of thrombus-containing stenoses and complete disappearance of intracoronary thrombus in all cases in which 150,000 U urokinase was locally infused over 30 minutes. There was no evidence of abrupt closure, distal embolization, or no reflow in any patient. CONCLUSIONS: Local urokinase delivery with the Dispatch catheter can result in rapid and complete intracoronary thrombolysis using substantially less drug than standard thrombolytic techniques. Intramural deposition of drug with this technique creates a local reservoir of urokinase that may provide prolonged thrombolytic activity at the infusion site.

Adult↗
PubMed1995

Primary angioplasty using a urokinase-coated hydrogel balloon in acute myocardial infarction during pregnancy.

A 38-year-old multigravid white female presented at 16 weeks gestation with an acute inferoposterolateral myocardial infarction. Emergent coronary angiography demonstrated a total proximal occlusion of a large dominant left circumflex artery with a filling defect at the site of the occlusion suggestive of thrombus. Primary angioplasty using a urokinase-coated hydrogel balloon resulted in successful recanalization of the vessel with restoration of normal TIMI Grade III flow and, most notably, apparent complete lysis of the intracoronary thrombus. After a subsequently uneventful pregnancy, a healthy baby was delivered.

Adult↗
PubMed1995

Recanalization of totally occluded saphenous vein grafts using local urokinase delivery with the Dispatch catheter.

Current techniques for the percutaneous revascularization of totally occluded vein grafts are limited by a low initial success rate, a significant incidence of distal embolization, and a high rate of early graft reclosure. This case report describes two patients in whom graft recanalization was attempted with the combined use of balloon angioplasty/intra-graft stent placement and local urokinase delivery using a new angiotherapy catheter. Successful recanalization was achieved in both patients without major complications, in spite of a large thrombus burden as demonstrated by angiography.

Angioplasty, Balloon, Coronary↗
PubMed1995

Quantitation of myocardial dysfunction in ischemic heart disease by echocardiographic endocardial surface mapping: correlation with hemodynamic status.

Autopsy studies have suggested that infarction of > 35% of the myocardium is associated with cardiogenic shock. However, the relation between the extent of myocardial dysfunction and hemodynamic status has not been defined in patients in vivo. This study investigated, in patients with short-term and chronic left ventricular dysfunction, the relation between hemodynamic status and the extent of regional dyssynergia measured by two-dimensional echocardiography with quantitative endocardial surface mapping. Sixty patients were classified into hemodynamic groups by pulmonary capillary wedge pressure and cardiac index. Two-dimensional echocardiograms were used to calculate left ventricular endocardial surface area index (ESAi), abnormal wall motion index (AWMi), percentage myocardial dysfunction (%MD), and number of wall motion abnormalities. All patients in class 4 (high pulmonary capillary wedge pressure and low cardiac index had > or = 60% MD. With univariate analysis, hemodynamic class correlated with ESAi, AWMi, %MD, the number of wall motion abnormalities, and two clinical variables (number of infarctions and use of diuretic agents). By stepwise linear regression, only AWMi and the number of infarctions were independently predictive of hemodynamic status.

Aged↗
PubMed1995

Percentage change rather than plasma level of LDL-cholesterol determines therapeutic response in coronary heart disease.

We have analysed 11 trials which used quantitative angiography to assess the effects of lipid-lowering therapy on coronary atherosclerosis. Linear regression, weighted for the number of patients studied, showed that the change in per cent diameter stenosis was significantly correlated with per cent reduction in LDL-cholesterol (r = 0.74, p < 0.0005), but not with the LDL-cholesterol concentration during the trials. These findings have important implications for the secondary prevention of coronary heart disease.

Anticholesteremic Agents↗
PubMed1994

Treatment of intracoronary thrombus with local urokinase infusion using a new, site-specific drug delivery system: the Dispatch catheter.

BACKGROUND: The presence of intracoronary thrombus significantly increases the risk of conventional balloon angioplasty because of a high incidence of abrupt closure, distal embolization, and no-reflow phenomenon. The purpose of this study was to assess a new technique for treating intracoronary thrombus consisting of the local delivery of urokinase directly to the angioplasty site with a novel, catheter-based, drug delivery system. METHODS: The Dispatch catheter is a new local, drug-delivery device that allows for the prolonged infusion of therapeutic agents at an angioplasty site while still maintaining distal coronary perfusion. Six patients with angiographic or clinical evidence of intracoronary thrombus were treated with 150,000 units of urokinase over a 30-min period using this device prior to or following conventional balloon angioplasty and/or directional atherectomy. RESULTS: Successful delivery of urokinase directly to the angioplasty site was achieved in all 6 patients without hemodynamic or electrocardiographic compromise. In all six cases, local urokinase therapy resulted in complete dissolution of angiographic intracoronary thrombus and/or reduction of the coronary stenosis. Limited ischemia due to side-branch occlusion by the catheter's coils was noted in one patient. Distal embolization or no-reflow phenomenon were not observed in any case. CONCLUSION: The local drug-delivery catheter used in this study was able to successfully and rapidly achieve intracoronary thrombolysis by delivering limited quantities of urokinase directly to the angioplasty site, while still maintaining distal coronary perfusion. This technique of local, thrombolytic drug delivery may be useful in the percutaneous treatment of intracoronary thrombus and thrombus-containing stenoses.

Aged↗
PubMed1994

Effect of low-grade conductive heating on vascular compliance during in vitro balloon angioplasty.

Radiofrequency-powered, thermal balloon angioplasty is a new technique that enhances luminal dilatation with less dissection than conventional angioplasty. The purpose of this study was to assess the effect of radiofrequency heating of balloon fluid on the pressure-volume mechanics of in vitro balloon angioplasty and to determine the histologic basis for thermal-induced compliance changes. In vitro, radiofrequency-powered, thermal balloon angioplasty was performed on 46 paired iliac segments freshly harvested from 23 nonatherosclerotic pigs. Balloon inflations at 60 degrees C were compared to room temperature inflations in paired arterial segments. Intraballoon pressure and volume were recorded during each inflation as volume infusion increased pressure over a 0 to 10 atm range. Pressure-volume compliance curves were plotted for all dilatations. Six segments were stained to assess the histologic abnormalities associated with thermal compliance changes. Radiofrequency heating acutely shifted the pressure-volume curves rightward in 20 of 23 iliac segments compared to nonheated controls. This increase in compliance persisted after heating and exceeded the maximum compliance shift caused by multiple nonheated inflations in a subset of arterial segments. Histologically, heated segments showed increased thinning and compression of the arterial wall, increased medial cell necrosis and altered elastic tissue fibers compared to nonheated specimens. In conclusion, radiofrequency heating of intraballoon fluid to 60 degrees C acutely increases vascular compliance during in vitro balloon angioplasty of nonatherosclerotic iliac arteries. The increased compliance persists after heating and can be greater than the compliance shifts induced by multiple conventional dilatations. Arterial wall thinning and irreversible alteration of elastic tissue fibers probably account for thermal compliance changes.

Angioplasty, Balloon↗
PubMed1994

Decreased platelet deposition and smooth muscle cell proliferation after intramural heparin delivery with hydrogel-coated balloons.

BACKGROUND: In vitro and in vivo studies have demonstrated both anticoagulant and antiproliferative effects of heparin. The purpose of this study was to assess the effect of local intramural delivery of heparin, using heparin-coated hydrogel balloons, on platelet deposition and early smooth muscle cell proliferation after in vivo balloon angioplasty. METHODS AND RESULTS: The effects of local heparin delivery were assessed during balloon angioplasty of porcine peripheral arteries. All balloon dilatations were performed with oversized hydrogel balloons coated with a known quantity of heparin. Balloon dilatations in contralateral vessels with uncoated hydrogel balloons served as study controls. The pharmacokinetics of heparin delivery were assessed using 3H-heparin to quantitate heparin wash-off from the balloon surface, heparin delivery to the arterial wall, and intramural persistence of drug. Platelet deposition at 1 hour after balloon injury was quantified using 111In-labeled platelets. Smooth muscle cell proliferation was assessed 6 to 7 days after angioplasty with immunohistochemical staining for proliferating cell nuclear antigen. 3H-heparin wash-off from the hydrogel balloon surface occurred rapidly, with approximately 95% of the heparin coating disappearing within 10 seconds in the intact circulation. Approximately 2% of heparin on the balloon surface was delivered intramurally at the time of angioplasty. Intramural heparin dissipated rapidly, although small amounts of intramural heparin could still be detected for at least 48 hours. In comparison to control vessels, there was less 111In-platelet deposition (P = .002) and less medial smooth muscle cell proliferation (P = .03) in heparin-treated vessels. CONCLUSIONS: Local intraluminal delivery of heparin at the time of balloon angioplasty with heparin-coated hydrogel balloons results in intramural deposition of drug that persists for at least 48 hours. This in vivo technique significantly decreases platelet deposition and early smooth muscle cell proliferation after angioplasty injury.

Angioplasty, Balloon↗
PubMed1994

Inhibition of platelet deposition and lysis of intracoronary thrombus during balloon angioplasty using urokinase-coated hydrogel balloons.

BACKGROUND: Conventional balloon angioplasty of intracoronary thrombus is associated with a high incidence of abrupt closure, distal embolization, and no-reflow phenomenon. The purpose of this study was to assess a new technique for treating intracoronary thrombus consisting of the local delivery of urokinase directly to the angioplasty site with urokinase-coated hydrogel balloons. METHODS AND RESULTS: We assessed local urokinase delivery using hydrogel balloons in four protocols. First, we evaluated the pharmacokinetics of urokinase delivery in vitro using 125I-labeled urokinase to measure drug loading onto hydrogel balloons, drug retention by the hydrogel polymer during blood exposure, and drug transfer from the balloon surface to the arterial wall during balloon dilatation. Second, we measured 125I-urokinase washoff from the hydrogel balloon in the intact circulation and intramural drug delivery during in vivo balloon angioplasty in 10 anesthetized New Zealand rabbits. Third, we assessed the effect of local urokinase delivery on 111In-labeled platelet deposition after balloon angioplasty in vivo in 13 porcine carotid or iliac arteries dilated with urokinase-coated balloons and compared them with contralateral control arteries dilated with saline-coated balloons. Finally, we determined the clinical efficacy of urokinase-coated balloons in 15 patients with intracoronary thrombus, including 7 who demonstrated abrupt thrombotic closure after conventional angioplasty. Between 241 and 1509 U urokinase could be loaded onto hydrogel balloons ranging in size from 2 to 8 mm. In vitro and in vivo studies demonstrated that hydrogel balloons absorbed significantly more urokinase and demonstrated less drug wash-off than nonhydrogel balloons (P < .01). Similarly, both in vitro and in vivo studies demonstrated urokinase transfer from the hydrogel to the arterial wall during balloon angioplasty, with greater intramural drug deposition with larger balloons (P < .01). Local urokinase delivery after in vivo porcine angioplasty decreased 111In-labeled platelet deposition by 47% compared with contralateral control vessels (P = .03). Use of urokinase-coated balloons in patients with intracoronary thrombus resulted in thrombus dissolution and reversal of abrupt closure in all cases, without evidence of distal embolization. CONCLUSIONS: With the use of hydrogel-coated balloons, urokinase can be delivered locally to an angioplasty site. This technique decreases platelet deposition after in vivo balloon angioplasty and is efficacious in treating intracoronary thrombus in patients, including those with abrupt thrombotic closure.

Adult↗
PubMed1993

In vivo radiofrequency thermal balloon angioplasty of porcine coronary arteries: histologic effects and safety.

The purpose of this study was to assess the safety and histologic effects of radiofrequency thermal balloon angioplasty in the coronary vasculature of normal pigs. Radiofrequency thermal balloon angioplasty was performed in 30 coronary arteries of 16 nonatherosclerotic pigs. Heated inflations were performed at either 50 degrees, 60 degrees, or 70 degrees C for 30 or 60 seconds, and were compared with five nonheated inflations in five additional arteries. All balloon inflations were performed at 2 atm pressure with a balloon/vessel diameter ratio of 1.2 to 1. Heart rate, arterial pressure, and left ventricular pressure were monitored continuously for each animal. A 12-lead ECG, coronary angiography, and two-dimensional transthoracic echocardiography were performed before and 1 hour after each balloon inflation. Each animal was subsequently put to death for postmortem cardiac examination. Heated inflations were well tolerated in 28 of the 30 arteries without significant adverse effects. During one inflation, ventricular fibrillation occurred because of prolonged ischemia from an occlusive guiding catheter. In another artery, a heated inflation resulted in a dissection with a transient decrease in distal coronary flow. Histologic examination revealed a significant increase in wall thinning and elastic fiber straightening with heating at 70 degrees C for both 30 and 60 seconds, and a significant increase in intracoronary thrombus with heating at 70 degrees C for 60 seconds. Depth of periarterial myocardial heat necrosis paralleled the increase in temperature, with an average depth of 166 microns at 50 degrees C, 312 microns at 60 degrees C, and 1031 microns at 70 degrees C. In vivo, radiofrequency coronary angioplasty can be performed relatively safely without significant electrical, hemodynamic, or ischemic changes beyond those seen with conventional nonthermal angioplasty. The extent of heat-induced vessel wall thinning, elastic tissue straightening, intracoronary thrombus formation, and periarterial myocardial necrosis are all related to balloon temperature or duration of heating.

Angioplasty, Balloon, Coronary↗
PubMed1989

Influence of fibrinolysis and percutaneous transluminal coronary angioplasty on the frequency of ventricular premature complexes.

This study evaluated the aggressive management of acute myocardial infarction to determine how it modifies the incidence of ventricular arrhythmias and of other determinants of prognosis during recovery. The population consisted of 344 consecutive survivors of acute myocardial infarction admitted to the hospital with chest pain and ST-segment elevation on the electrocardiogram. Three groups constituted the study population: 168 control patients treated conservatively or in whom fibrinolysis was unsuccessful, 73 patients successfully reperfused with intravenous streptokinase and 103 patients with both successful fibrinolysis and successful percutaneous transluminal coronary angioplasty (PTCA) of the artery responsible for the infarct. Early spontaneous angina occurred in 47 control patients (28%), 25 streptokinase patients, (34%) and, in significantly fewer number, 20 PTCA patients (19%, p less than 0.05). Similarly, exercise-induced ST-segment depression on the predischarge exercise treadmill test was less frequent with PTCA (p less than 0.05). The number of ventricular premature complexes (VPCs) on a 24-hour Holter recording was 40 +/- 123/hr in the control group and significantly less in the streptokinase (21 +/- 64, p less than 0.05) and PTCA groups (17 +/- 61, p less than 0.05). Three or more VPCs/hr were observed in 50% of the control patients, compared with 29% of the streptokinase and 27% of the PTCA patients (p less than 0.005). Mean radionuclide ejection fraction was greater than 40% and similar in the 3 study groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗
PubMed1989

Limited usefulness of intermittent nitroglycerin patches in stable angina.

The efficacy of continuous and intermittent nitroglycerin patches (10 mg/day) was compared in a randomized, placebo-controlled trial in 36 patients with stable angina and reproducible, exercise-induced ST depression. Intermittent treatment was administered either 18 or 14 h/day with an intermission of 6 h or 10 h, respectively. Exercise tests were performed during the last 2 h of patch application. Compared with placebo, neither continuous nitroglycerin nor the two intermittent regimens prolonged total treadmill time or time to 1 mm ST depression. No treatment eliminated exercise-induced ST depression in greater than 1 of the 36 patients. Time to angina was prolonged (by 40 +/- 66 s) only during the "10 h off" treatment (p = 0.001); time to angina increased by greater than or equal to 20% in 13 patients. Responders to treatment could be predicted by a short history of angina (p less than 0.05) and a time to angina less than or equal to 250 s during the placebo test. For each treatment, greater than or equal to 25 of the patients reported headache; 4 additional patients dropped out because of severe headache and 2 others because of a coronary event in a washout period. Thus, in most patients with stable angina, side effects outweight any benefit demonstrable with this therapy.

Administration, Cutaneous↗
PubMed1989

Exercise-induced myocardial ischemia in a cold environment. Effect of antianginal medications.

The influence of cold on the threshold for myocardial ischemia and the efficacy of antianginal drugs in a cold environment were assessed in 24 patients with stable angina and exercise-induced ST depression. Treadmill exercise tests were done according to a randomized double-blind protocol 90 minutes after administration of placebo, 80 mg propranolol, or 120 mg diltiazem, each at both -8 degrees and 20 degrees C. Eight of the patients were classified by history as cold-sensitive before the study. For the entire group, none of the exercise end points differed significantly between cold and normal temperatures with placebo. However, cold-sensitive patients developed 1 mm ST depression 30% sooner (169 +/- 41 versus 244 +/- 38 seconds, p less than 0.01) at -8 degrees C compared with 20 degrees C. At the onset of ischemia, rate-pressure product was lower in the cold (19.8 +/- 1.0 versus 22.0 +/- 1.6 x 10(-3), p less than 0.05). Both propranolol and diltiazem prolonged time to onset of 1 mm ST depression at both temperatures. The magnitude of improvement at -8 degrees C was equal to that at 20 degrees C, and differences between the two drugs were not statistically significant. Only diltiazem prolonged total exercise duration. Thus, as assessed by exercise testing, cold does not worsen ischemic threshold in most stable angina patients. However, in a subgroup identifiable by history, ischemic threshold is lower in the cold. Propranolol and diltiazem are as effective for exercise-induced ischemia in a cold environment as at normal temperatures.

Angina Pectoris↗