Intra-aortic Balloon Research Articles

Is an Integrated Approach Warranted for Concomitant Carotid and Coronary Artery Disease?

Background. The management of patients with severe, concomitant coronary and carotid artery occlusive disease is controversial. Methods. Between 1975 and 1996, 512 patients (mean age, 64.9 years; 70% male) were admitted for coronary revascularization; 316 (61.7%) had asymptomatic, severe carotid disease (stenosis >70%) and 196 (38.3%) had symptomatic carotid disease (159 [31.1%] with transient ischemia and 37 [7.2%] with completed stroke). In group 1, coronary revascularization and carotid endarterectomy were simultaneously performed in 255 patients (49.8%) with unstable angina. In group 2 (staged approach), carotid endarterectomy was performed before coronary revascularization in 257 patients (50.2%) without unstable angina. Results. Before 1986, the incidence of stroke and death was greater in group 1 (n = 149) than in group 2 (n = 156) (14 [9.4%] versus 4 [2.6%]; p < 0.01). Since 1986, outcomes in group 1 (n = 106) and group 2 (n = 101) have been similar for stroke (2 [1.9%] versus 2 [2.0%]), death (4 [3.8%] versus 3 [3.0%]), and myocardial infarction (4 [3.8%] versus 5 [5.0%]). Significant univariate and multivariate predictors of adverse outcome were primarily heart-related (reoperation, intraaortic balloon use, ejection fraction <0.50, and angina grade 4 for death; age >70 years and congestive heart failure for stroke). Conclusions. Despite highly selected populations, contemporary surgical results do not indicate that staged treatment of severe, concomitant coronary and carotid artery occlusive disease has an advantage over simultaneous treatment. Advances in myocardial protection and perioperative hemodynamic management may account for the low incidences of stroke and death in these operations.

Effects of intra-aortic balloon occlusion on hemodynamics during, and survival after cardiopulmonary resuscitation in dogs.

To evaluate the effect of balloon occlusion of the proximal descending aorta during cardiopulmonary resuscitation (CPR) on hemodynamics, restoration of spontaneous circulation, and 24-hr survival. Prospective, randomized, controlled trial. Experimental laboratory in a university hospital. Eighteen anesthetized dogs. INTERVENTIONS; Catheters were placed for hemodynamic and blood gas monitoring. An aortic balloon catheter was placed with its tip just distal to the left subclavian artery. After 10 mins of ventricular fibrillation without CPR, 3 mins of Basic Life Support (chest compressions and ventilation with 100% oxygen) was followed by up to 30 mins of Advanced Cardiac Life Support with canine drug dosages. In the treatment group (n = 8), the intra-aortic balloon was inflated when Advanced Cardiac Life Support started and not deflated until shortly after restoration of spontaneous circulation. The control animals (n = 10) were treated with an identical resuscitation but without intra-aortic balloon occlusion. In the treatment group, coronary perfusion pressure was greater during Advanced Cardiac Life Support (p = .026). Restoration of spontaneous circulation was more frequent (7/8 dogs) as compared with the control group (3/10 dogs) (p = .025). There was a trend toward greater 24-hr survival in the treatment group (5/8 dogs) than in the control group (3/10 dogs). Balloon occlusion of the proximal descending aorta during experimental CPR improves restoration of spontaneous circulation. Further laboratory and human studies are needed to determine the clinical efficacy of this technique.

Mechanical methods of improving blood flow during cardiopulmonary resuscitation

Mechanical measures intended to increase blood flow to vital organs are the mainstay of therapy for patients in cardiac arrest. Several new cardiopulmonary resuscitation techniques and devices have been developed and tested since the first report of manual closed-chested cardiopulmonary resuscitation nearly four decades ago. These include vest cardiopulmonary resuscitation, active compression-decompression cardiopulmonary resuscitation, an intra-aortic perfusion balloon pump, and an inspiratory impedance threshold valve, interposed abdominal counterpulsation cardiopulmonary resuscitation, and phased thoracic-abdominal compression and decompression. Many of these new mechanical advances in the treatment of cardiac arrest are currently undergoing clinical evaluation in patients in cardiac arrest. Although some of those new methods and techniques have shown promise in small human clinical trials, none have yet to be found to be conclusively superior to manual closed-chested cardiopulmonary resuscitation.

Working pressure for full balloon inflation during intraaortic balloon pumping.

With changes in heart rate and mean aortic pressure, an intraaortic balloon (IAB) works with incomplete inflation. The effects of initial peak positive pressure and plateau holding positive pressure on IAB volume were investigated and minimum pressures necessary to inflate an IAB to a desired volume were established with a standard IAB catheter (Datascope type, 9.5 Fr, 40 ml). Initial peak pressure greater than 200 mm Hg was adequate to attain the desired volume of the IAB. Plateau positive pressure should be altered in accordance with hemodynamic changes.

Effect of additional intraaortic balloon support during weaning from a left ventricular assist system.

A safe and reliable method of weaning from a left ventricular assist system (LVAS) is necessary for successful circulatory support in patients with marginal heart failure. The purpose of this study is to assess the effect of additional intraaortic balloon (IAB) support during weaning from an LVAS by means of the LV pressure-volume relationship. A pneumatic LVAS with a sac-type blood pump was implanted in six adult mongrel dogs weighing 14 to 20 kg. All dogs had a drainage cannula placed in the left atrium and an outflow conduit in the ascending aorta. Hemodynamic parameters, pulmonary arterial flow, and pump output were monitored. An IAB was inserted through the groin. A conductance catheter and microtip manometer were inserted into the LV cavity. As a combination driving mode, LVAS ejection in the early diastolic phase and IAB inflation in the late diastolic phase were applied. After evaluation of baseline LV function, the pressure-volume relationship was repeatedly measured during change of driving modes as isolated LVAS, LVAS + IAB (1:1), LVAS + IAB (2:1), and isolated IAB supports. Finally, LV failure was introduced by stepwise ligation of left coronary arteries, and the LV pressure-volume relationship was measured in each driving mode. Under normal conditions, the pressure-volume loop showed no significant change among the four driving modes. In contrast, the LV pressure-volume relationship significantly improved according to the degree of additional IAB support on LVAS assistance under the condition of LV failure. These results suggest that additional IAB support might improve LV energy during weaning from an LVAS.

A NEW METHOD FOR RAPID, PERCUTANEOUS, SHEATH‐LESS INSERTION OF THE INTRA‐AORTIC BALLOON

SUMMARY Rapid insertion of the intra‐aortic balloon (IAB) via the femoral artery is sometimes necessary. The increasing age of patients in cardiac units means that insertion into atherosclerotic and stenosed vessels can lead to ischaemic complications, particularly when the sheath is used. We present a modified method for rapid, percutaneous insertion of the sheathless IAB using the sheath dilator supplied with the insertion kit.

Artéria radial na ampliação do uso de enxertos arteriais para revascularização do miocárdio: considerações anatômicas e tática cirúrgica

A artéria radial (AR) foi estudada sob o ponto de vista anatômico, histológico, imunohistoquímico e ultramicroscópico. Paralelamente, foram analisados os resultados de seu emprego na revascularização do miocárdio de 269 pacientes. No total, 319 artérias coronárias foram revascularizadas pela AR. Houve predomínio do sexo masculino (80,7%) e da raça branca (93,7%). A artéria torácica interna esquerda (ATIe) foi empregada em 246 pacientes. Outros 17 já haviam sido previamente revascularizados com a ATIe, perfazendo um total de 97,8%. A artéria torácica interna direita (ATId) foi empregada em 59 (21,9%) pacientes, a artéria gastroepiplóica direita (AGEd) em 17 (6,3%) pacientes e em 161 (59,8%) foram também realizadas 1 a 4 pontes de veia safena. A média de enxertos por paciente foi de 3,4. Não houve complicações isquémicas ou infecciosas no membro em que a AR foi retirada. Os estudos imuno-histoquímicos e ultramicroscópicos permitiram observar o grande espessamento da membrana limitante elástica interna da AR e o predomínio de fibras colágenas sobre as elásticas na camada média. As principais complicações pósoperatórias foram a fibrilação atrial em 21 (7,8%) pacientes, insuficiência respiratória em 21 (7,8%), alterações no ECG e/ou elevação de CKMB em 12 (4,5%) pacientes. O balão intra-aórtico foi utilizado em 6 (2,2%) pacientes. O cateterismo no pós-operatório precoce foi realizado em 21 pacientes. Em 1 paciente houve dissecção sem oclusão do óstio da AR pelo cateter, 1 (4,7%) apresentou sinais de espasmo da AR; nos demais a AR encontrava-se pérvia e sem lesões. Houve 6 (2,2%) óbitos hospitalares, sendo 3 por acidente vascular cerebral, 2 por baixo débito cardíaco e 1 paciente teve morte súbita. Nos últimos meses temos visado à revascularização miocárdica com o emprego máximo de enxertos arteriais. Como tática especial usamos a AR para anastomoses seqüenciais com as artérias de parede inferior e lateral do ventrículo esquerdo. A anastomose do coto proximal é realizada na ATIe que, por sua vez, é habitualmente anastomosada ao ramo interventricular anterior (RIA). As artérias AGEd e ATId in situ ou, como enxerto livre, têm complementado o procedimento. Dentre 64 pacientes operados nos últimos 3 meses com a utilização da AR, 62 (96,9%) receberam pelo menos 2 enxertos arteriais, 27 (42,2%) receberam pelo menos 3 enxertos arteriais e 8 (12,5%) pacientes receberam 4 ou 5 enxertos arteriais. Em 29 (45,3%) deles a AR foi anastomosada à ATIe ou ATId. Acreditamos que essa técnica reduza a excessiva pressão conseqüente à anastomose direta da AR na aorta e que o maior fluxo decorrente das anastomoses seqüenciais auxilie na manutenção da perviabilidade da AR. A despeito de considerarmos o enxerto pediculado da ATIe o principal método de revascularização do miocárdio, os resultados preliminares indicam que a AR constitui uma excelente via complementar na busca da revascularização completa do miocárdio com enxertos arteriais.

Changes of intraaortic balloon volume during pumping in a mock circulation system.

The effects of hemodynamic changes on intraaortic balloon (IAB) volumes were studied experimentally using a helium tachometer in a mock circulatory system. The IAB volume decreased with increases in the heart rate and mean aortic pressure, but the degree of reduction in the IAB volume was different among 4 commercially available IAB drivers. Improvements in IAB consoles are needed to compliment the progress made in percutaneous techniques for IAB insertion resulting in smaller balloons.

Mechanism of the Antiischemic Effect of Mibefradil, a Selective T Calcium Channel Blocker in Dogs: Comparison with Amlodipine

Calcium channel blockers are active in variant angina principally by preventing coronary vasospasm. However, a direct antiischemic effect may also occur. In open-chest dogs, an attack of variant angina was mimicked by a 2-min critical coronary stenosis, and the following reversible myocardial ischemia was assessed by measuring the decrease of segmental shortening. We compared the antiischemic mechanism of mibefradil, a T and L calcium channel blocker, with that of amlodipine, a pure L channel blocker. Both drugs showed a similar relationship between the decrease of the rate-pressure product and the antiischemic effect, but only mibefradil reduced heart rate. Amlodipine and mibefradil at the highest doses tested (20 and 70 micrograms/kg/min, respectively) restored 68 +/- 8 and 76 +/- 5% of segmental shortening in the ischemic area, respectively, as compared with preischemic values. Matching blood pressure (by intraaortic balloon) or heart rate (by atrial pacing) to predrug values showed that the antiischemic effect was mainly afterload-dependent for amlodipine and heart rate-dependent for mibefradil. We conclude that in variant angina, in addition to their antivasospastic effects, calcium channel blockers may be antiischemic by a direct myocardial effect associated with a decrease of the rate pressure product. Blockade of the T channel does not seem to participate in the direct antiischemic effect of mibefradil but could explain the decrease of heart rate.

Diabetes Mellitus and Morbidity and Mortality Risks after Coronary Artery Bypass Surgery

Of 1025 patients (912 men, 113 women) who underwent coronary artery bypass grafting and were followed up for a mean of 7.4 years, 45 (4.4%) had diabetes mellitus. Norwegian population is 1.8-2%). Early mortality was not significantly greater among diabetics than in non-diabetics (2.2 vs. 3.1%, odds ratio--OR-0.44, confidence interval--CI- 0.05-3.56). Diabetic patients had no increased risk of perioperative myocardial infarction (OR = 0.87, CI 0.36-2.10) or of low-output syndrome necessitating intraortic balloon pumping (OR = 0.42, CI 0.55-3.05), and no excess incidence of late non-fatal myocardial infarction (relative risk = 0.69, CI 0.10-1.28) or late chronic heart failure (OR = 2.50, CI 0.5-11.0). Long-term mortality was increased in the diabetic patients (relative risk 1.87, CI 1.60-2.14). Thus diabetes did not entail heightened risk of early mortality, perioperative myocardial infarction or low-output syndrome. Nor was there excess risk of recurrent angina pectoris, late non-fatal myocardial infarction or chronic heart failure among the diabetic patients, but the late mortality risk was increased.

Cardiac transplantation: An eight-year experience

From June 1985 to June 1993, a total of 199 orthotopic (2 retransplanted) and one heterotopic cardiac transplants were performed in patients whose ages ranged from 17to 66(average 53)years. There were 175 (87.5%) males and 25 (12.5%) females. The aetiology of end-stage heart disease included: ischaemic heart disease 138 (69%); idiopathic cardiomyopathy 53 (26.5%); valvular disease 7 (3.5%); and adriamycininduced cardiomyopathy in 2 (1%). At the time of surgery, 56 (26.5%) patients were in United Network for Organ sharing (UNOS) Status I (ICU, intra-aortic balloon other assists, inotropic support) and 144 (72%) were UNOS Status II. The majority of donors were local or within the state. Two immunosuppressive protocols have been utilised, viz., conventional triple drug therapy and OKT3 induction. The mean rejection has been 2.5 episodes/patient. The majority of these episodes, (72 %) occurred within the first three months. Of the 1.8 infectious episodes per patient, opportunistic organisms predominated with a 98 per cent recovery. We have experienced 53 postoperative deaths. Currently, 147 (73.5%) recipients are alive and well. Our one-year actuarial survival is approximately 82per cent, the five year figure being 64 per cent. Tampa General Hospital is, at present, one of the most active cardiac transplant centres in the USA. Our eightyear experience has allowed us to mature through our learning curve to become an established, successful cardiac transplant program.

Experience with warm blood cardioplegia in 480 patients

From 1 March 1992 too 31 July 1993 (17 months), 480 consecutive patients underwent various open-heart procedures under anterograde (83 patients) or retrograde (397 patients) continuous warm blood cardioplegia. Some 352 patients (73.3%) had isolated coronary artery bypass grafts (CABG) and 117 (24.3%) had valve replacement either isolated (96) or in combination with other operations (21). Two patients had CABG and ventricular aneurysmectomy, eight had correction of congenital defects, and one had resection of left atrial myxoma. The 30-day postoperative mortality rate was 2.9% (14 deaths). In four patients the cause of death was not cardiogenic. An intra-aortic balloon was used in 11 patients following CABG (3.1%) with six survivors. Perforation of the coronary sinus occurred in one patient. Perioperative myocardial infarction was observed in 5.6% of patients after CABG. No myocardial infarction occurred after valve replacement. Phrenic nerve injury and wound infection were not observed. These results indicate that warm blood cardioplegia, especially when delivered retrogradely, provides excellent myocardial protection of both ventricles during various open-heart procedures.

Experience with Warm Blood Cardioplegia in 480 Patients

From 1 March 1992 too 31 July 1993 (17 months), 480 consecutive patients underwent various open-heart procedures under anterograde (83 patients) or retrograde (397 patients) continuous warm blood cardioplegia. Some 352 patients (73.3%) had isolated coronary artery bypass grafts (CABG) and 117 (24.3%) had valve replacement either isolated (96) or in combination with other operations (21). Two patients had CABG and ventricular aneurysmectomy, eight had correction of congenital defects, and one had resection of left atrial myxoma. The 30-day postoperative mortality rate was 2.9% (14 deaths). In four patients the cause of death was not cardiogenic. An intra-aortic balloon was used in 11 patients following CABG (3.1%) with six survivors. Perforation of the coronary sinus occurred in one patient. Perioperative myocardial infarction was observed in 5.6% of patients after CABG. No myocardial infarction occurred after valve replacement. Phrenic nerve Injury and wound infection were not observed. These results indicate that warm blood cardioplegia, especially when delivered retrogradely, provides excellent myocardial protection of both ventricles during various open-heart procedures.

Prevention of left ventricular thrombus formation during pneumatic pump assist

A postcardiotomy patient with a pneumatic pulsatile pump for left ventricular assist showed a smoke-like swirling echo within the left ventricle during pump assist. The image disappeared partially during intra-aortic balloon pumping, which was performed as usual. Subsequently, three pumps (native left ventricle, pneumatic and intra-aortic balloon) were driven synchronously: that is, the ventricular assist pump ejected the blood in the first half of the diastole of the native heart beat, and the intra-aortic balloon was inflated during the second half. With this bisected diastolic driving, the abnormal echo disappeared completely. The patient died 52 days after operation, but no thromboembolic episode was observed during the course, and no fresh thrombus was found within the left ventricle at autopsy. The bisected diastolic driving method served as an aid to prevent stagnation of blood and thrombus formation within the native left ventricle in this patient with a left ventricular assist device.

New Algorithm of Intra Aortic Balloon Pumping in Patients With Atrial Fibrillation

New Algorithm of Intra Aortic Balloon Pumping in Patients With Atrial Fibrillation

New Algorithm of Intra Aortic Balloon Pumping in Patients With Atrial Fibrillation

Intra aortic balloon pumps have been operated inaccurately when used in patients with atrial fibrillation. In 36 pre-operative cardiac surgical patients with atrial fibrillation, the interval between the R wave of the electrocardiogram and the dicrotic notch (R-DCN interval) of the aortic pressure waveform showed significant correlation with the preceding R-R interval by second degree polynomial curves (0.53 < r2 < 0.74, p < 0.01). Based on these results a new algorithm for atrial fibrillation was designed. During brief off periods of the intra-aortic balloon pump in atrial fibrillation, electrocardiograms and aortic pressure waveforms were simultaneously recorded and analyzed to obtain a second degree polynomial curve between the preceding R-R and R-DCN intervals. The precise timing of balloon inflation was controlled using the equation in response to the preceding R-R interval. This new algorithm showed the smallest time lags (SD = 8.5 msec) when compared to other existing algorithms (the Kontron model-10, 53.49 msec; the Aries Medical model-700, 43.69 msec; the Datascope system-90, 25.98 msec; the Mansfield 3000, 19.65 msec; and the Kontron K-2000, 14.89 msec) in mock simulation driving using data obtained from clinically recorded waveforms.

Intra-aortic Balloon Counterpulsation as a ‘Bridge’ to Cardiac Transplantation: Effects in Nonischemic and Ischemic Cardiomyopathy

Intra-aortic balloon (IAB) counterpulsation has been utilized as an effective "bridge" to transplantation in patients with end-stage heart failure. To determine if patients with heart failure with nonischemic cardiomyopathy (NICM) derive the same benefit from IAB support as those with ischemic cardiomyopathy (ISCM), we evaluated 27 patients with NICM and 16 patients with ISCM who required IAB support while awaiting transplantation. Hemodynamic changes, effects on organ function (renal and hepatic), frequency of complications, and clinical outcomes were analyzed. Baseline demographics and hemodynamics were comparable in both groups (p = NS). Hemodynamics improved in both groups, immediately (15 to 30 min) following IAB insertion, with greater improvement (p < 0.05) in cardiac index and a trend toward greater reduction in filling pressures in the NICM group. Systemic vascular resistance fell to a similar degree in both groups. During continued IAB support (0.13 to 38 days in NICM, 1 to 54 days in ISCM), all hemodynamic changes persisted in both groups, with larger decrease (p < 0.05) in systemic vascular resistance and greater increase (p < 0.05) in cardiac index in the patients with NICM. The reduction in filling pressures, however, tended to be greater in patients with ISCM. Renal and hepatic function parameters improved to a similar extent in both groups. The frequency of complications and clinical outcome during IAB support were also similar in the two groups. These data confirm that IAB counterpulsation is a safe and effective "bridge" in patients with both NICM and ISCM with end-stage heart failure. The mechanism of sustained benefit in the two groups, however, may be different; afterload reduction appears to be more important in patients with NICM whereas reduction in filling pressures (increased coronary perfusion pressure) may be the main mechanism in patients with ISCM.

Is there a place for cold crystalloid cardioplegia in the 1990s?

New cardioplegic techniques have been advocated as advantageous when compared with previously accepted standard methods. This study assessed results of a recent cohort of 388 consecutive patients undergoing coronary artery bypass grafting between 1990 and 1992 using a standard cold crystalloid cardioplegia. The mean age of patients was 61.0 ± 0.5 years; there were 324 male and 64 female patients. Risk factor distribution has not changed recently. Preoperative left ventricular dysfunction (grade III/IV) was significant in 35.1% of patients, and 63.3% had previous myocardial infarctions. Intraoperative cardiac arrest was achieved using an average of 1,254 ± 14 mL of St. Thomas' solution in multiple doses. Patients had a mean of 3.1 ± 0.04 grafts constructed, with 87.7% receiving at least one internal thoracic artery graft. Anoxia and total cardiopulmonary bypass times were 40.6 ± 0.6 and 90.3 ± 1.4 minutes, respectively. Perioperative myocardial infarction was identified in 5.7% of patients with elevated creatine kinase levels and electrocardiographic measurement changes, inotropic agents were required in 17.8%, and the intraaortic balloon was required in 3.6% of patients. Hospital stays averaged 11.2 ± 0.5 days. Overall 30-day mortality was 1.0%, whereas those patients undergoing elective operation (n = 219) had a mortality of 0%. In conclusion, cold crystalloid cardioplegia has the advantages of being inexpensive and simple to use. These results suggest that coronary artery bypass grafting still may be performed very safely using this technique.

Early and late results following emergency isolated myocardial revascularization during hypothermic fibrillatory arrest

From January, 1982, through November, 1985, 127 consecutive patients had emergency isolated myocardial revascularization during hypothermic fibrillatory arrest. Mean age was 62.3 years; 27 patients (21.2%) were older than 70 years. Mean ejection fraction was 0.49, with 20 (15.7%) less than 0.35. Intraaortic balloons were present in 109 patients (85.8%). Nitroglycerin was given therapy had been used in 12 patients (9.4%). Indications intravenously to 97 patients (76.3%), and thrombolylic for operation were postinfarction ischemia in 61 patients (48.0%), preinfarction unstable angina in 44 (34.6%), acute ischemia following failed percutaneous angioplasty in 14 (11.0%), and cardiogenic shock in 8 (6.3%). Operation was performed within 1 week of an acute infarction in 47 patients. Mean number of graftsper patientwas 4.1. There was 1 hospital death (0.8%) and l perioperative myocardial infarction (0.8%). Actuarial survival at 45 months was 90.8 ± 2.9%. Mean New York Heart Association Classification for the 117 long-term survivors was 1.12.

Attenuation of myocardial stunning by the ACE inhibitor ramiprilat through a signal cascade of bradykinin and prostaglandins but not nitric oxide.

Attenuation of myocardial stunning by several angiotensin-converting enzyme (ACE) inhibitors has been demonstrated. However, the signal cascade mediating such protective effect has not been analyzed in detail so far. In a first protocol, we addressed the role of bradykinin and analyzed the effect of the ACE inhibitor ramiprilat without and with added bradykinin B2 receptor antagonist HOE 140 on regional myocardial blood flow (colored microspheres) and function (sonomicrometry). Thirty-two enflurane/N2O-anesthetized open-chest dogs were subjected to 15 minutes of occlusion of the left circumflex coronary artery (LCx) and 4 hours of subsequent reperfusion. Eight dogs served as placebo controls (group 1), and 8 dogs received ramiprilat (20 micrograms/kg IV) before LCx occlusion (group 2). Eight dogs received a continuous intracoronary infusion of HOE 140 [0.5 ng/(mL.min) IC] during ischemia and reperfusion (group 3), and in 8 dogs HOE 140 was infused continuously during ischemia and reperfusion, starting 45 minutes before the administration of ramiprilat (group 4). Mean aortic pressure was kept constant with an intra-aortic balloon, and heart rate did not change throughout the experimental protocols. Under control conditions and during myocardial ischemia, posterior transmural blood flow (BF) and systolic wall thickening (WT) were not different in the four groups of dogs. However, at 4 hours of reperfusion, WT was still depressed in groups 1 (-10 +/- 20% of control [mean +/- SD]), 3 (-18 +/- 12% of control), and 4 (-12 +/- 21% of control), whereas WT in group 2 had recovered to 55 +/- 20% of control (P < .05 versus group 1). BF at 4 hours of reperfusion was not different in the four groups of dogs. Thus, the beneficial effect of ramiprilat on the functional recovery of stunned myocardium was obviously mediated by bradykinin. Since bradykinin stimulates the formation of both prostaglandins and nitric oxide, we tested in a second protocol which of these mediators was further involved in the beneficial effects of ramiprilat. Twenty-four additional dogs were subjected to 15 minutes of LCx occlusion and 4 hours of reperfusion. Six dogs received the cyclooxygenase inhibitor indomethacin (10 mg/kg IV) (group 5) and 6 dogs a combination of indomethacin with ramiprilat (group 6) before LCx occlusion. Six dogs received the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (20 mg/kg IV) (group 7) and 6 dogs a combination of L-NAME with ramiprilat (group 8) before LCx occlusion. BF and WT before and during myocardial ischemia were not different in groups 5 and 6 and groups 7 and 8. However, at 4 hours of reperfusion, WT was still depressed in groups 5 (-10 +/- 38% of control), 6 (-7 +/- 18% of control), and 7 (-12 +/- 14% of control), whereas WT in group 8 had recovered to 47 +/- 28% of control (P < .05 versus group 7). BF at 4 hours of reperfusion was not different in the four groups of dogs. In summary, the attenuation of stunning by the ACE inhibitor ramiprilat involves a signal cascade of bradykinin and prostaglandins but not nitric oxide.