Stefan H.J. Monnink

RETRANSFUSION OF SUCTIONED BLOOD DURING CARDIOPULMONARY BYPASS IMPAIRS HEMOSTASIS

In a previous study we observed extensive clotting and fibrinolysis in blood from the thoracic cavities during cardiopulmonary bypass. We hypothesized that retransfusion of this suctioned blood could impair hemostasis. In this prospective clinical study we investigated the effect of suctioned blood retransfusion on systemic blood activation and on postoperative hemostasis. During coronary artery bypass grafting in 40 patients, suctioned blood was collected separately. It then was retransfused to the patient at the end of the operation (n = 19), or it was retained (n = 21). During the study, 12 consecutive patients, randomized in two groups of 6, were analyzed for biochemical parameters indicating blood activation and clotting. The immediate and significant increase in circulating concentrations of thrombin-antithrombin III complex, tissue-type plasminogen activator, fibrin degradation products, and free plasma hemoglobin demonstrated the effect of suctioned blood retransfusion. Moreover, the increased concentrations of thrombin-antithrombin III complex and fibrin degradation products indicated renewed systemic clotting and fibrinolysis as a direct result of the retransfusion of suctioned blood. Concentrations of all indicators mentioned remained significantly lower in the retainment group. The clinical data showed that retainment of suctioned blood resulted in significantly decreased postoperative blood loss (822 mL in the retransfusion group versus 611 mL in the retainment group; p < 0.05) and similar or even reduced consumption of blood products (513 versus 414 mL red blood cell concentrate and 384 versus 150 mL single-donor plasma; both not significant). We conclude that retransfusion of highly activated suctioned blood during cardiopulmonary bypass exacerbates wound bleeding.

Comparison of zofenopril and lisinopril to study the role of the sulfhydryl-group in improvement of endothelial dysfunction with ACE-inhibitors in experimental heart failure

We evaluated the role of SH‐groups in improvement of endothelial dysfunction with ACE‐inhibitors in experimental heart failure. To this end, we compared the vasoprotective effect of chronic treatment with zofenopril (plus SH‐group) versus lisinopril (no SH‐group), or N‐acetylcysteine (only SH‐group) in myocardial infarcted (MI) heart failure rats. After 11 weeks of treatment, aortas were obtained and studied as ring preparations for endothelium‐dependent and ‐independent dilatation in continuous presence of indomethacin to avoid interference of vasoactive prostanoids, and the selective presence of the NOS‐inhibitor L‐NMMA to determine NO‐contribution. Total dilatation after receptor‐dependent stimulation with acetylcholine (ACh) was attenuated (−49%, P<0.05) in untreated MI (n=11), compared to control rats with no‐MI (n=8). This was in part due to impaired NO‐contribution in MI (−50%, P<0.05 versus no‐MI). At the same time the capacity for generation of biologically active NO after receptor‐independent stimulation with A23187 remained intact. Chronic treatment with n‐acetylcysteine (n=8) selectively restored NO‐contribution in total dilatation to ACh. In contrast, both ACE‐inhibitors fully normalized total dilatation to ACh, including the part mediated by NO (no significant differences between zofenopril (n=10) and lisinopril (n=8)). Zofenopril, but not lisinopril, additionally potentiated the effect of endogenous NO after A23187‐induced release from the endothelium (+100%) as well as that of exogenous NO provided by nitroglycerin (+22%) and sodium nitrite (+36%) (for all P<0.05 versus no‐MI). We conclude that ACE‐inhibition with a SH‐group has a potential advantage in improvement of endothelial dysfunction through increased activity of NO after release from the endothelium into the vessel wall. Furthermore, this is the first study demonstrating the selective normalizing effect of N‐actylcysteine on NO‐contribution to ACh‐induced dilatation in experimental heart failure.

Endothelial Dysfunction in Patients With Coronary Artery Disease: A Comparison of Three Frequently Reported Tests

Background Endothelial dysfunction is useful in predicting future cardiovascular disease. At present several tests are available to test endothelial function: coronary diameter response to acetylcholine, forearm bloodflow (FBF) response to acetylcholine, and brachial artery flow-mediated dilative (FMD) response to postischemic hyperemia. This study aimed to compare the three most frequently reported endothelial function tests. Methods Twenty-eight patients (19 males and nine females, mean age 57 years) referred for diagnostic coronary angiography were considered for endothelial function measurement in the coronary artery as well as in the forearm by FBF and FMD. Results Acetylcholine decreased the mean coronary diameter by 7.4% (SD 6.3%) and increased the mean FBF by 230% (SD 152%). Hyperemia increased the mean brachial diameter by 6.7% (SD 4.8%). The effect of acetylcholine on forearm resistance vessels was significantly related to the effect of acetylcholine on the coronary conduit vessels (P=0.039). Nonetheless, FMD was not related to FBF nor to the coronary response. Conclusion In patients with mild coronary endothelial dysfunction, forearm vasoreactivity is related to the coronary response, provided that the same stimulus is used.

Minimally invasive coronary artery bypass grafting versus coronary angioplasty for isolated type C stenosis of the left anterior descending artery

BACKGROUND Isolated stenosis of the left anterior descending coronary artery can be treated with medication, percutaneous transluminal coronary angioplasty, or coronary artery bypass grafting. Recently a new treatment has been developed, which is called minimally invasive direct coronary artery bypass grafting. This new treatment is a modification of the conventional bypass operation and is performed through a small anterolateral thoracotomy without cardiopulmonary bypass. METHODS To compare minimally invasive bypass with angioplasty, we evaluated in-hospital results and 1-year follow-up in 181 consecutive patients with isolated type C stenosis of the left anterior descending coronary artery between January 1995 and July 1996. Of these patients, 71 underwent minimally invasive bypass and 110 angioplasty. Preoperative characteristics were not significantly different between the two groups. RESULTS In-hospital death, periprocedural myocardial infarction, emergency reoperation by means of conventional coronary bypass grafting, use of an intraaortic balloon pump, and cerebrovascular accidents were not significantly different between the two groups. At 1-year follow-up, survival was not significantly different in the two groups (minimally invasive bypass 95.7% +/- 0.2% vs angioplasty 95.3% +/- 0.2%; p = 0.89), whereas freedom from repeated revascularization was significantly more common in the group undergoing minimally invasive bypass (bypass 96.9% +/- 0.2% vs angioplasty 67.6% +/- 0.5%; p < 0.001). This study shows that the need for repeated revascularization, and therefore the use of health care resources, is significantly less with minimally invasive bypass than with angioplasty in patients with isolated type C stenosis of the left anterior descending coronary artery.

Exercise-induced ischemia after successful percutaneous coronary intervention is related to distal coronary endothelial dysfunction

Background As endothelial dysfunction can be responsible for myocardial ischemia even in the absence of significant coronary lesions, we aimed to assess the correlation between endothelium-dependent vasomotor function and inducible ischemia late after successful coronary angioplasty. Methods In 30 patients without angiographic restenosis or coronary disease progression, coronary endothelial function was determined by acetylcholine infusion 6 months after elective single-vessel stenting of the left coronary artery. Acetylcholine-induced diameter changes were assessed in the proximal and distal segments of both the stented and the contralateral vessels by means of quantitative coronary angiography. A maximal workload ergometric test was also performed prior to endothelial function testing. Results Acetylcholine induced significant vasoconstrictive responses in the distal but not in the proximal segments of both the stented (-11 ± 7% versus baseline; p < .01) and the contralateral vessels (-11 ± 6%; p < .01), which were significantly correlated (R = .48; p < .05) and were completely reverted by nitroglycerine. Inducible ischemia was the only predictive factor for distal vasoconstriction in the stented vessel (p < .01) but not in the contralateral vessel (p = .06). Patients with minor signs of ischemia at the ergometric test showed a greater vasoconstriction than those with a completely normal test (-16 ± 7% versus -7 ± 6%; p < .01). Conclusions Exercise-induced ischemia late after successful percutaneous coronary intervention is related to distal coronary endothelial dysfunction.

Coronary vasomotor response is related to the angiographic extent of coronary sclerosis in patients with stable angina pectoris

Disturbed vasomotor function in coronary arteries has clinical importance in early stages of coronary artery disease (CAD), as it may contribute to the potential risk for an ischaemic coronary event. In the present study, we have investigated the relationship between coronary vasomotor function and the extent of CAD. The response to acetylcholine and nitrate infusion was assessed by quantitative coronary angiography. The extent of CAD was categorized into two groups: minor CAD (normal coronary arteries and vessel wall irregularities) and significant CAD (one-, two- and three-vessel disease). A total of 277 patients with stable angina pectoris, referred for a first diagnostic coronary angiography, were eligible for analysis (mean age 57 years, 61% male). The response to nitrate was significantly impaired in patients with significant CAD ( P <0.001). On the other hand, the response to acetylcholine was not different between the two groups ( P =0.12); however, a trend between the response to acetylcholine and the extent of CAD was observed in patients without a previous infarction ( P =0.07), which was a significant interaction variable. Furthermore, a significant relationship between coronary vasomotor response and the number of cardiovascular risk factors was observed ( P <0.05). In conclusion, in a heterogeneous group of patients, coronary vasomotor function measured by nitrate infusion was more strongly associated with the extent of CAD and the number of risk factors than the response to acetylcholine. These data suggest that, in patients with advanced atherosclerosis or multiple risk factors, the vasomotor dysfunction is not solely restricted to the endothelium.

Prior Cytomegalovirus Infection Does Not Predict Clinical Outcome after Percutaneous Transluminal Coronary Angioplasty

Background: A direct association between human cytomegalovirus (HCMV) infection and the development of restenosis after coronary angioplasty has been suggested. The aim of this prospective study was to evaluate the value of HCMV serology in predicting the clinical outcome after percutaneous transluminal coronary angioplasty (PTCA). Methods and Results: 112 patients undergoing elective PTCA were included in the study. HCMV antibody levels were measured by ELISA. Cardiac events within a follow-up period of 6 months after PTCA were defined as (1) progression or recurrence of anginal complaints and/or a positive exercise test; (2) restenosis that required repeat revascularization. 73% of PTCA patients were seropositive for HCMV. Successful PTCA was achieved in a total of 94 patients, who were followed for 6 months. In 31/94 patients (33%) cardiac events occurred and in 15/94 (16%), this could be related to restenosis. We found no statistically significant difference between seropositive and negative patients with respect to anginal complaints or the need for revascularization. There was no evidence of acute reactivation, since titers of anti-HCMV antibodies did not increase after PTCA. Conclusion: This study shows that the clinical outcome after PTCA is not related to the HCMV serostatus of the patient. Therefore, our data do not support the hypothesis that serological markers of HCMV infection are of clinical importance for the assessment of a patient’s individual risk after PTCA. This does not preclude a role for local reactivation of HCMV at the site of angioplasty.

Coronary Vascular Function in Stable and Unstable Angina

Angina pectoris and acute myocardial infarction are the main cardiac manifestations of atherosclerosis. Atherosclerosis is a pathological condition that underlies several important disorders including coronary artery disease, cerebrovascular disease, and diseases of the aorta and peripheral arterial circulation. Since Edward Jenner first attributed angina pectoris to coronary artery disease in 1786, there is a growing understanding about the pathophysiology of coronary artery disease and its complications. The first coronary artery disease manifestation in women is more likely to be angina, whereas in men it more often presents as a myocardial infarction. Even after surviving the acute stage of myocardial infarction, the incidence of re- infarction, sudden death, angina pectoris and cardiac failure are all substantial. Further innovations in diagnosis and treatment of coronary disease will undoubtedly improve the outlook of patients surviving the initial attack.