Infarct size reduction with coronary venous retroinfusion of diltiazem in the acute occlusion/reperfusion porcine heart model.

Calcium channel blockers are commonly used for the treatment of ischemic heart disease, but their effects on myocardial infarct size (IS) after reperfusion are not well known. Enflurane-anesthetized open-chest pigs subjected to 60-min left anterior descending coronary artery (LAD) occlusion followed by 3-h reperfusion were referred to one of the four experimental groups. Beginning 10 min before the onset of reperfusion, pigs in group A received diltiazem (7.5 micrograms/kg/min) retrogradely infused into the coronary vein for 30 min. In group B, the same amount of diltiazem was infused into the right atrium. A corresponding volume of saline was infused into the coronary vein in group C or into the right atrium in group D. IS expressed as a percentage of the myocardium at risk was significantly smaller (p < 0.01) in group A (33 +/- 14%; mean +/- SD) than in groups B (58 +/- 11%), C (58 +/- 11%), and D(63 +/- 10%). After reperfusion, functional recovery of the ischemic myocardium, determined by ultrasound crystals, was significantly more improved (p < 0.05) in group A as compared with other groups. The ischemic and nonischemic regional myocardial blood flow (RMBF), determined by radioactive microspheres, did not differ between four groups. Coronary venous retroinfusion of diltiazem had a myocardial protective effect in the porcine experimental model of acute coronary occlusion/reperfusion, whereas intravenous drug administration was not effective. The protective effect could not be attributed to washout of toxic metabolites from the ischemic area or to improved microcirculation. It was probably related to a pronounced accumulation of the calcium-channel blocker diltiazem in the ischemic myocardium achieved by the coronary venous route of delivery.

Short-term synchronized retroperfusion before reperfusion reduces infarct size after prolonged ischemia in dogs.

BACKGROUND: Previous studies have demonstrated that synchronized coronary venous retroperfusion (SRP) can restore blood flow to the ischemic myocardium, resulting in infarct size reduction and improvement of the left ventricular function. Despite the nutritive blood flow achieved by SRP being relatively limited, SRP has been shown to improve washout of by-products from the ischemic myocardium. The aim of this study was to investigate whether short-term SRP immediately prior to reperfusion would attenuate the deteriorative phenomena following reperfusion. METHODS AND RESULTS: Closed-chest anesthetized dogs underwent 3 hours of left anterior descending coronary artery (LAD) occlusion. The dogs were then randomized into two groups: (1) control group (n = 9), in which the occlusion was immediately followed by 3-hour reperfusion; or (2) SRP group (n = 9), in which SRP was started 3 hours after occlusion and maintained for 30 minutes with sustained occlusion followed by 2.5-hour reperfusion with simultaneous discontinuation of SRP. There were no statistical differences between the groups in global hemodynamics and degree of ischemia measured by radiolabeled microspheres. Myocardial infarct size (triphenyltetrazolium method) expressed as percentage of risk area was significantly smaller in the SRP group (24 +/- 7%, mean +/- SEM) than in the control group (54 +/- 9%). The extent of myocardial hemorrhage expressed as percentage of infarct size was also significantly reduced in the SRP group (3 +/- 2%) compared with the control group (24 +/- 6%). The increase in end-diastolic wall thickness in the ischemic area after reperfusion assessed by two-dimensional echocardiography was significantly less in the SRP group. Blood flow measurements after reperfusion demonstrated the occurrence of no-reflow phenomenon only in the control group. Histological examination revealed extensive myocardial hemorrhages only in the control group, which extended into the nonnecrotic myocardium in four of nine hearts and extensive contraction band necrosis compared with the SRP group. CONCLUSIONS: Short-term SRP prior to reperfusion can reduce infarct size, myocardial hemorrhage, wall swelling, and no-reflow phenomenon. The mechanism of this beneficial effect is not clear but might be due to gradual reperfusion and washout of by-products from the ischemic myocardium before fully oxygenated arterial blood reperfusion.

Local beta-adrenergic blockade does not reduce infarct size after coronary occlusion and reperfusion: a study of coronary venous retroinfusion of metoprolol.

Previous studies have demonstrated pronounced ischemic zone myocardial concentrations of metoprolol following coronary venous retroinfusion in pigs with coronary artery ligation. The effect of coronary venous retroinfusion of metroprolol on myocardial infarct size was studied in 16 pentobarbital-anesthetized open-chest pigs undergoing 60-minute occlusion of the left anterior descending coronary artery followed by 3 hours of reperfusion. Pigs in the experimental group (n = 8) were given 0.4 mg/kg (1.0 mg/ml) of metroprolol via the anterior interventricular vein over a period of 5 minutes, beginning immediately after coronary occlusion followed by 0.2 mg/kg/hr intravenously. Control pigs (n = 8) received the same volume of saline as the treated group. The risk area and the necrotic area were assessed by monastral blue dye and triphenyl tetrazolium chloride staining, respectively. Metoprolol did not influence hemodynamics. Plasma concentrations of metoprolol were within therapeutic levels. The administration of the beta-blocker resulted in a trend toward reduced norepinephrine concentrations, both in the aorta and coronary vein after coronary occlusion, but it did not prevent norepinephrine overflow following reperfusion. Infarct size expressed as a percentage of the risk area was 77 +/- 11% in the control group and 75 +/- 12% (mean +/- SD; NS) in the treated group. Thus, metoprolol retroinfusion did not reduce infarct size and did not prevent catecholamine overflow after reperfusion. It is concluded that the beneficial effects of metroprolol in acute infarction are probably unrelated to local beta-adrenergic blockade, at least in the pig, an animal with a paucity of coronary collateral blood flow.

Preservation of regional myocardial ultrasonic backscatter and systolic function during brief periods of ischemia by synchronized coronary venous retroperfusion.

This study examines the effects of brief periods of ischemia on average and cardiac cycle-dependent variation of regional ultrasonic backscatter paralleled with changes in regional myocardial contraction, and to what extent these changes could be reversed by synchronized coronary venous retroperfusion. In five closed-chest dogs, the left anterior descending coronary artery was occluded on four occasions for a 2-minute period and retroperfusion was applied randomly to two of the coronary occlusions. Complete functional recovery was allowed between the occlusions. Two-dimensional echocardiographic images were obtained before and at the peak of the 2-minute occlusion period. Regional myocardial contraction as measured by fractional area change and systolic wall thickening during untreated occlusions decreased from 33.9 +/- 14.0% to -0.15 +/- 6.2%, and from 22.0 +/- 1.8% to -17.9 +/- 2.2%, whereas during retroperfusion-treated occlusions it changed from 37.4 +/- 8.5% to only 23.4 +/- 11.2% (p less than 0.005 versus baseline), and from 24.1 +/- 2.8% to only 12.7 +/- 2.0% (p less than 0.005 versus baseline), corresponding to a preservation of 62% and 52% of baseline regional contraction, respectively. Average regional gray level (arbitrary units) during untreated coronary occlusions exhibited a significant increase in the ischemic regions, from 5.6 +/- 2.7 at baseline to 11.5 +/- 4.4 during occlusion (p less than 0.005); during retroperfusion-treated occlusions, average gray level increased from 4.7 +/- 3.6 to only 6.3 +/- 3.6 (NS). Untreated coronary artery occlusions resulted in a systolic increase in gray level in the ischemic region, followed by a diastolic decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

Differences in infarct size with lidocaine as compared with bretylium tosylate in acute myocardial ischemia and reperfusion in pigs.

The effects of the antiarrhythmic drugs lidocaine and bretylium tosylate on myocardial necrosis were studied in anesthetized pigs subjected to 60-min coronary occlusion followed by 3-h reperfusion. Group A (n = 7) received lidocaine (average dose +/- SD = 1,828 +/- 515 mg) before and during coronary occlusion and after reperfusion; the other series (group B, n = 7) received bretylium tosylate (3,457 +/- 1,323 mg). Infarct size was 16.3 +/- 14.7% in the lidocaine group as compared with 68.6 +/- 12.6% (p less than 0.01) in the bretylium group. In vitro release of superoxide anion from porcine granulocytes was studied using the lucigenin-dependent chemiluminescence technique. Lidocaine significantly reduced the peak chemiluminescence response to zymosan from 3.34 +/- 0.44 without lidocaine to 2.23 +/- 0.46 (p less than 0.01) and 1.06 +/- 0.17 mV (p less than 0.001), with lidocaine concentrations of 20 and 200 micrograms/ml, respectively. Bretylium had no effect on the chemiluminescence response. Adherence of porcine granulocytes to plastic was also reduced from 332 +/- 32 cells/mm2 (no lidocaine) to 247 +/- 35 and 206 +/- 26 cells/mm2 with lidocaine concentrations of 20 and 200 micrograms/ml, respectively (p less than 0.001). Bretylium had no significant effect. Eight additional bretylium-treated pigs received either rabbit antiporcine granulocyte serum (group C, n = 4) to reduce circulating granulocytes or nonimmune serum (group D, n = 4). Infract size in the granulocyte-depleted pigs was 26.6 +/- 5.6% as compared with 51.4 +/- 5.5% in pigs that received nonimmune serum (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Retrograde coronary venous administration of recombinant tissue-type plasminogen activator: a unique and effective approach to coronary artery thrombolysis.

Recent studies of interventional therapy by way of the coronary venous system have demonstrated that it can protect acutely ischemic myocardium. To evaluate the efficacy of coronary venous retroinfusion compared with systemic intravenous administration of recombinant tissue-type plasminogen activator (rt-PA), 14 dogs were studied with a copper coil-induced thrombus in the left anterior descending coronary artery. The rt-PA (24,000 fluorescence units/kg) was administered continuously, either intravenously (n = 8) or retrogradely (n = 6), for 30 min beginning 60 min after coronary occlusion. Thrombolysis was determined by repetitive coronary angiography. All dogs were killed 3 h after termination of rt-PA infusion and infarct size was measured by the triphenyltetrazolium chloride staining technique. Complete thrombolysis occurred in five of the six dogs in the retroinfusion group and four of the eight dogs in the systemic intravenous infusion group. Partial lysis was achieved in two dogs treated by intravenous infusion. Lysis did not occur in one dog treated with retroinfusion and in two dogs treated with intravenous infusion. Time to thrombolysis was 13.4 +/- 2.3 min in the retroinfusion group versus 27.8 +/- 4.8 min in the intravenous group (p less than 0.001). Myocardial functional recovery in the ischemic zone measured by two-dimensional echocardiography 60 min after reperfusion was significant only in the retroinfusion group (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetic analysis of coronary venous retroinfusion: a comparison with anterograde coronary artery drug administration using metoprolol as a tracer.

Plasma and myocardial tissue concentrations of metoprolol were studied in ischemic and nonischemic areas of 22 pigs after 90 (n = 19) and 16 (n = 3) min of left anterior descending coronary artery occlusion. Group A (n = 6) received simultaneous intravenous metoprolol (0.2 mg/kg body weight) and tritium-labeled (3H)-metoprolol (0.2 mg/kg) retrogradely into the coronary vein. In group B (n = 5), metoprolol and 3H-metoprolol were administered in the same way, but at half the volume to study the influence of derived coronary venous pressure on the myocardial concentration of drug. In group C (n = 3), metoprolol was given retrogradely and saline solution was infused into the left anterior descending artery before induced death to wash out metoprolol from the coronary veins. To rule out a possible influence of the development of myocardial necrosis on drug distribution, metoprolol was retroinfused after 1 min of arterial occlusion in three pigs (group D). In group E (n = 5), metoprolol (0.2 mg/kg) was infused anterogradely into the left anterior descending artery. Peak plasma concentration was significantly higher after intravenous infusion of metoprolol (1,188 +/- 503 nmol/liter) than after coronary venous infusion (417 +/- 155 nmol/liter; p less than 0.001). In groups A and B, the nonischemic myocardial concentration of metoprolol was 250 to 300 pmol/g, whether the drug was infused intravenously or into the coronary vein. Coronary venous retroinfusion, however, resulted in a substantial accumulation of metoprolol in the ischemic myocardium. In group A pigs, subendocardial myocardial concentration was 16,800 +/- 7,774, mid-myocardial 39,590 +/- 18,043 and subepicardial 57,143 +/- 29,030 pmol/g (mean +/- SE). The ischemic myocardial concentration in pigs from group B was somewhat less pronounced, probably secondary to a lower coronary venous pressure (15 +/- 3 mm Hg) with the lower volume of infusion (6.1 +/- 0.3 ml) in group B compared with 32 +/- 5 mm Hg with a 14 +/- 1 ml infusion in group A. Coronary artery anterograde administration resulted in myocardial ischemic and nonischemic zone drug concentrations similar to those observed after retroinfusion into the coronary vein. With both modes of administration, there was a transmyocardial gradient from a somewhat lower drug concentration in the subendocardium, toward an increasing level in the mid-myocardium, to the highest concentration in the subepicardial zone of the ischemic myocardium. Coronary venous retroinfusion resulted in pronounced drug accumulation in the ischemic myocardium. The derived coronary venous pressure during infusion influenced the concentration of drug.(ABSTRACT TRUNCATED AT 400 WORDS)

Coronary venous retroinfusion of deferoxamine reduces infarct size in pigs.

The efficacy of coronary venous retroinfusion of the iron chelator deferoxamine was studied in 24 pentobarbital-anesthetized open chest pigs with a 60 min occlusion of the left anterior descending coronary artery followed by 3 h of reperfusion. Eight retrogradely treated pigs were given 10 mg/kg body weight of deferoxamine by way of the anterior interventricular vein and eight systemically treated pigs received the same doses of deferoxamine intravenously. Drug infusions lasted for 5 min, beginning 15 min before reperfusion. Eight control pigs received systemic intravenous saline solution. Myocardial area at risk and necrotic area were assessed by the monastral blue dye and the triphenyltetrazolium chloride staining method, respectively. There were no significant differences in hemodynamics or regional myocardial function (sonomicrometry) among the groups. Infarct size expressed as percent of risk area was 73.9 +/- 13.5% in the control group, 70.6 +/- 16.4% in the systemically treated group and 48.5 +/- 21.4% (p less than 0.05) in the retrogradely treated group. In conclusion, deferoxamine significantly reduced infarct size after coronary occlusion only when given regionally by way of the coronary vein. Because there was no significant hemodynamic effect caused by deferoxamine infusion, it is suggested that this drug prevents postischemic reperfusion injury by a direct cardioprotective effect.

Positron emission tomography demonstrates that coronary sinus retroperfusion can restore regional myocardial perfusion and preserve metabolism.

Positron emission tomography was used to image blood flow and metabolic tracers in risk zone myocardium after left anterior descending coronary artery occlusion during synchronized coronary venous retroperfusion. Six control and seven intervention open chest dogs had occlusion of the mid left anterior descending coronary artery. Synchronized retroperfusion commenced 25 min later. Flow tracers (rubidium-82 and nitrogen-13 ammonia) were injected retrogradely. Three hours after coronary occlusion, fluorine-18 (F-18) deoxyglucose uptake in the control and treatment groups was compared. At 200 min of occlusion, infarct size was assessed. Retrograde flow tracer uptake was observed in the risk zone in the seven intervention dogs. Fluorine-18 deoxyglucose uptake in the risk zone was increased in five of the six intervention dogs but was reduced in five of the six control dogs. The risk zone to normal zone F-18 deoxyglucose count ratio was higher in the intervention than the control group (1.13 +/- 0.39 vs. 0.59 +/- 0.51; p less than 0.05). The endocardial subsegment risk zone to normal zone F-18 deoxyglucose count ratio was also significantly higher in the intervention group. Percent infarction in the risk zone was 70% lower in the group treated with synchronized retroperfusion than in the control group (18.4 +/- 22.6% vs. 61.2 +/- 25.4%; p less than 0.02). Thus, positron emission tomography revealed that retroperfusion could deliver oxygenated blood and maintain metabolism in risk zone myocardium. Infarct size was limited to 30% of that of control. In acute closure of the left anterior descending coronary artery, synchronized retroperfusion might be considered for maintaining viability of the jeopardized myocardium if the artery cannot be reopened rapidly.

Synchronized coronary venous retroperfusion for support and salvage of ischemic myocardium during elective and failed angioplasty.

To determine the safety and efficacy of synchronized coronary venous retroperfusion during brief periods of ischemia, 30 patients undergoing angioplasty of the left anterior descending coronary artery were studied. Each patient underwent a minimum of two angioplasty balloon inflations. Alternate dilations were supported with retroperfusion; the unsupported inflations served as the control inflations. Synchronized retroperfusion was performed by pumping autologous femoral artery blood by means of an electrocardiogram-triggered retroperfusion pump into the great cardiac vein through a triple lumen 8.5F balloon-tipped retroperfusion catheter inserted percutaneously from the right internal jugular vein. Clinical symptoms, hemodynamics and two-dimensional echocardiographic wall motion abnormalities were analyzed. Retroperfusion was associated with a lower angina severity score (0.8 +/- 1 vs. 1.2 +/- 1) and delay in onset of angina (53 +/- 31 vs. 37 +/- 14 s; p less than 0.05) compared with the control inflations. The magnitude of ST segment change was 0.11 +/- 0.14 mV with retroperfusion and 0.16 +/- 0.17 mV without treatment (p less than 0.05). The severity of left ventricular wall motion abnormality was also significantly (p less than 0.01) reduced with retroperfusion compared with control (0.7 +/- 1.4 [hypokinesia] vs. -0.3 +/- 1.6 [dyskinesia]). There were no significant changes in hemodynamics, except in mean coronary venous pressure, which increased from 8 +/- 3 mm Hg at baseline to 13 +/- 6 mm Hg with retroperfusion. Four patients required prolonged retroperfusion for treatment of angioplasty-induced complications. The mean retroperfusion duration in these patients was 4 +/- 2 h (range 2 to 7). In the three patients who underwent emergency bypass surgery, the coronary sinus was directly visualized during surgery and found to be without significant injury. There were no major complications. Minor adverse effects were transient atrial fibrillation (n = 2), jugular venous catheter insertion site hematomas (n = 4) and atrial wall staining (n = 1), all of which subsided spontaneously. Thus, retroperfusion significantly reduced and delayed the onset of coronary angioplasty-induced myocardial ischemia and provided effective supportive therapy for failed and complicated angioplasty.

Percutaneous cooling of ischemic myocardium by hypothermic retroperfusion of autologous arterial blood: effects on regional myocardial temperature distribution and infarct size.

The effects of synchronized coronary venous retroperfusion of cooled autologous arterial blood on regional myocardial temperature distribution and infarct size were studied in open chest dogs with 3.5 h of left anterior descending coronary artery occlusion. After 30 min of occlusion, the dogs were randomly assigned to one of three groups: 1) untreated control group (n = 5), 2) normothermic retroperfusion group (infusion temperature 32 degrees C) (n = 7), and 3) hypothermic retroperfusion group (infusion temperature 15 degrees C) (n = 7). Regional myocardial temperatures were measured by using needle-tipped thermistors stabbed in the 1) anterior wall distal to the occlusion site, 2) anterior wall proximal to the occlusion site, 3) left lateral wall, 4) posterior wall, and 5) right ventricular free wall. Rectal and pulmonary artery temperatures were also measured. In the hypothermic retroperfusion group, the anterior wall temperature decreased rapidly by 5 degrees C at 15 min of retroperfusion (p less than 0.05 vs. normothermic retroperfusion or untreated control groups), whereas the temperature at other sites decreased with a linear trend over time. Myocardial temperatures in the ischemic area (distal anterior wall) were generally lower than those in the other sites during the first 60 min of hypothermic retroperfusion and the largest intramyocardial temperature difference (3.6 degrees C) was found at 15 min after retroperfusion. Infarct size expressed as a percent of the risk area was significantly smaller in the hypothermic retroperfusion group (6.2 +/- 3.3%) than in the control (64.9 +/- 14%) or normothermic retroperfusion groups (24.1 +/- 6.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Beneficial effects of coronary venous retroinfusion but not left atrial administration of superoxide dismutase on myocardial necrosis in pigs.

The efficacy of coronary venous versus left atrial administration of superoxide dismutase was studied in 24 open chest pigs which had 60 min of left anterior descending coronary artery occlusion followed by 3 h reperfusion. The pigs were randomly assigned to three treatment protocols: group A (n = 8) superoxide dismutase (5 mg kg-1) was infused into the great cardiac vein for 30 min beginning 15 min before reperfusion; group B (n = 8) superoxide dismutase (5 mg kg-1) was infused into the left atrium in a similar manner to group A; group C (n = 8) bovine serum albumin (5 mg kg-1) was infused into the great cardiac vein in the same manner as group A. Infarct size, expressed as percent of area at risk, was significantly smaller in group A (28.2 +/- 13.0%) than groups B (58.7 +/- 8.3%) and C (61.6 +/- 7.2%) (P less than 0.05). The results indicate that retroinfusion of superoxide dismutase into the great cardiac vein before reperfusion may be an effective treatment for the prevention of reperfusion injury, even in the absence of a well developed coronary collateral circulation. Antegrade (left atrial) administration of the same amount of superoxide dismutase did not decrease infarct size in pigs. The most likely explanation for this difference in efficacy is that drug delivery with left atrial administration is dependent on antegrade flow with reperfusion which is less reliable and less efficient than coronary venous retroinfusion. The latter provides a predictably high concentration of superoxide dismutase to the jeopardized myocardium during the period of ischaemia before reperfusion.

Historical vignette celebrating the 30th anniversary of diagnostic ambulatory electrocardiographic monitoring and data reduction systems.

The ambulatory electrocardiographic (ECG) monitor is a device developed approximately 30 years ago to detect, locate and document hemodynamic insufficiency states in target organs with compromised regional arterial circulations. These insufficiency states are usually silent until they are suddenly precipitated by secondary remote, hemodynamically significant cardiac arrhythmias, hypotensive states caused by internal hemorrhage or reduced cardiac output including cardiogenic shock. Insufficiency events cause serious regional dysfunction, resulting in transitory or permanent damage of the remote target organs (brain, heart, splanchnic and renal) often causing paralytic ileus, gangrene of the gut or rectum, myocardial infarction or cerebral stroke. Comprehensive experimental studies conducted in the author's laboratory over a period of years (1946-1971) proved that such remote ischemic states are often recurrent and can cause serious, irreparable damage, but whenever the cause of the regional ischemic state was treated promptly it could reverse the insufficiency state. Practical ambulatory ECG diagnostic monitors and data reduction systems were developed to diagnose these elusive precipitating pathophysiologic events that might coincide with the patient's symptoms and thus determine the most appropriate preventive therapy.

Overestimation of myocardial infarct size by histologic measurement in a model of occlusion followed by reperfusion.

We studied 32 transverse left ventricular slices of myocardium from 16 pigs after 45 to 100 minutes of coronary artery occlusion followed by 180 minutes of reperfusion. Infarct area for each slice was determined as follows: (1) grossly, by triphenyl tetrazolium chloride staining of each slice, and (2) microscopically, by complete histologic sectioning of the triphenyl tetrazolium chloride-stained surface of each slice. Planimetry of necrotic and nonnecrotic areas was performed from tracings and photographs of triphenyl tetrazolium chloride-stained slices and from actual histologic sections. When triphenyl tetrazolium chloride and histologic measurements were compared, necrotic tissue area had decreased 11.4% +/- 15.0% (2.59 +/- 1.04 vs 2.09 +/- 0.86 cm2). Nonnecrotic tissue area decreased 20.6% +/- 24.0% (8.31 +/- 3.79 vs 5.16 +/- 2.73 cm2). In this model of ischemia followed by reperfusion, with fixation and processing, viable tissue shrank almost twice as much as necrotic tissue. This differential shrinkage introduces an error resulting in overestimation of infarct size by histologic quantitation.

More rapid thrombolysis with coronary venous retroinfusion of streptokinase compared with intravenous administration. An experimental study in canines.

The efficacy of coronary venous retroinfusion vs intravenous administration of streptokinase was compared in 20 closed chest dogs with copper coil induced thrombosis of the left anterior descending coronary artery. Streptokinase was continuously infused for 60 min (100 IU kg-1 min-1) starting 60 min after coronary artery occlusion. Time to clot lysis was determined by coronary angiography performed at 5 min intervals. Complete lysis occurred in eight out of 10 dogs receiving intravenous streptokinase and in all 10 dogs in the coronary venous group. Time to thrombolysis was significantly shorter with coronary venous retroinfusion (23 +/- 8 min) than after systemic infusion (62 +/- 26 min; P less than 0.001). Recovery of ischaemic zone left ventricular systolic function, studied by two-dimensional echocardiography, was significantly better in the animals that received retrograde streptokinase than in the group that received intravenous streptokinase (17 +/- 12% vs -2 +/- 16%; P less than 0.05). Myocardial necrosis expressed as a percentage of the risk area was 8 +/- 12% after retroinfusion of streptokinase compared with 32 +/- 25% (P less than 0.005) after intravenous administration. In conclusion, coronary venous administration of streptokinase was more effective than intravenous therapy as determined by more rapid clot lysis which resulted in improved functional recovery of the ischaemic myocardium and a significant reduction in myocardial necrosis.

Reversal of chronic regional myocardial dysfunction (hibernating myocardium) by synchronized diastolic coronary venous retroperfusion during coronary angioplasty.

A 62 year old man with previous myocardial infarction, an occluded right coronary artery and a 90% stenosis of the left anterior descending coronary artery underwent angioplasty with the support of coronary venous retroperfusion of arterial blood during the procedure. In two of four angioplasty balloon dilations of the left anterior descending coronary artery, synchronized diastolic retroperfusion of the coronary veins with arterial blood was applied to protect the severely dysfunctioning myocardium from additional ischemia. Two-dimensional echocardiography was used to monitor and quantitate alterations in left ventricular function. Retroperfusion of arterial blood resulted in immediate improvement in ischemic zone wall motion despite the totally occluded artery during balloon dilation. Echocardiographic images recorded after angioplasty showed a marked improvement in contraction of the previously dyskinetic segments, with changes similar to those seen during balloon dilations with synchronized diastolic coronary venous retroperfusion. Thus, in this patient, viability of chronically dysfunctioning myocardium could be demonstrated by the improvement in regional wall motion during retroperfusion. This technique could eventually be of value to elucidate the anatomic location of viable myocardium while maintaining adequate left ventricular systolic function during coronary artery interventions in the catheterization laboratory.