H.Storm Floten

Vascular endothelial growth factor-mediated, endothelium-dependent relaxation in human internal mammary artery

BACKGROUND Vascular endothelial growth factor (VEGF) has been shown to have potential to treat ischemic diseases. Moreover, its vasorelaxing or vasodilatory effect might be favorable for relieving graft spasm. In this study, we examined the vasorelaxing effects of recombinant VEGF in isolated human internal mammary artery (IMA) and compared the responses to acetylcholine and nitroglycerin. METHODS Isometric tension of IMA ring segments was measured with an organ bath technique. With an optimal resting tension determined from its individual length-tension curve, precontraction was induced by 10(-8) M U46619 and cumulative concentration-relaxation was measured by application of VEGF (10(-12) to 10(-15) M), acetylcholine (10(-10) to 10(-5) M), and then nitroglycerin (10(-4.5) M). RESULTS Vascular endothelial growth factor induced concentration-dependent relaxation (EC50: -9.89+/-0.05 log M; Emax: 63.2%+/-7.3%) in IMA with intact endothelium. The relaxant responses to VEGF were significantly attenuated by pretreatment with Nomega-nitro-L-arginine (L-NNA) alone and indomethacin + L-NNA, and totally abolished by removal of the endothelium or pretreatment with indomethacin + L-NNA + oxyhemoglobin. Internal mammary arteries became more sensitive to VEGF in the presence of indomethacin alone. However, acetylcholine-induced relaxation was not abolished by treatment with indomethacin + L-NNA + oxyhemoglobin (Emax: 16.9%+/-2.7%). The endothelium-independent relaxations induced by nitroglycerin were also significantly inhibited by administration of oxyhemoglobin. CONCLUSIONS The results demonstrate that VEGF-induced endothelium-dependent relaxation in the human IMA is mainly due to nitric oxide release. Although the vasorelaxing effect is not the primary advantage of this drug when it is used for angiogenesis, such effect may be advantageous in patients who also need a coronary artery bypass operation.

Interaction between vasodilators and vasopressin in internal mammary artery and clinical significance

BACKGROUND Arginine vasopressin (AVP) has recently been demonstrated as an alternative in the treatment of severe refractory vasodilatation in coronary artery bypass grafting. However, AVP may be a spasmogen for graft spasm. We compared the in vitro antispastic effect among calcium-channel antagonists (nifedipine, diltiazem, and verapamil), nitroglycerin, and the highly selective AVP (V1) receptor antagonist [1-deaminopenicillamine, 4-valine, 8-D-arginine] vasopressin. METHODS Human internal mammary artery segments (n = 218) were studied in organ baths. The inhibitory effects of the above vasodilators on AVP-mediated contraction were studied in two ways: relaxation with AVP precontraction and depression of the AVP-induced contraction after pretreatment with vasodilators. RESULTS All three calcium-channel antagonists caused limited relaxation (18.3%+/-5.4% for nifedipine, n = 11; 22.2%+/-3.8% for verapamil, n = 10; and 26.2%+/-7.5% for diltiazem, n = 9). The plasma concentration of calcium-channel antagonists had no significant depression effect on the AVP-induced contraction. In contrast, [1-deaminopenicillamine, 4-valine, 8-D-arginine] vasopressin caused full (100%, n = 11) and nitroglycerin caused nearly full (93%+/-3%, n = 10) relaxation. Pretreatment with [1-deaminopenicillamine, 4-valine, 8-D-arginine] vasopressin (10(-8), 10(-7), or 10(-6) mol/L, respectively) significantly increased the effective concentration for 50% of the AVP-induced contraction (10(-8.6)+/-10(0.1) mol/L, p = 0.009; 10(-7.8)+/-10(0.07) mol/L, p = 0.000; or 10(-6.9)+/-10(0.11) mol/L, p = 0.000 versus the control, 10(-9.24)+/-10(0.16) mol/L). However, nitroglycerin only slightly depressed the AVP-induced contraction. CONCLUSIONS [1-Deaminopenicillamine, 4-valine, 8-D-arginine] vasopressin may provide specific antispastic effect in either prophylaxis or treatment of the AVP-related vasospasm in the internal mammary artery. Nitroglycerin may be effective in treatment but has little effect on prophylaxis. Use of calcium-channel antagonists may have little benefit in AVP-related vasospasm.

Five-year results of coronary bypass grafting for patients older than 70 years: Role of internal mammary artery

Despite numerous references to the superiority of the internal mammary artery (IMA) over the saphenous vein for myocardial revascularization, its role in the elderly is still in question. From January 1984 through December 1988, 1,081 patients older than 70 years (mean age, 74.9 years) underwent bypass grafting, 354 (33%) receiving left IMA grafts based on the surgeons preference and 727 (67%) receiving vein grafts only. Selection bias resulted in a higher incidence of known risk factors (such as cardiomegaly, arrhythmias, left ventricular failure, wall motion abnormalities, and preoperative combined New York Heart Association/Canadian Cardiovascular Association functional class IV) in patients in whom the IMA was not used. However, unstable angina, acute myocardial infarction, left ventricular dysfunction, and left main disease were not contraindications for using IMA grafts. The operative mortality rate was significantly lower in IMA patients (2.8% versus 7.6%). The actuarial 5-year survival rate (standard error) was higher in patients with IMA grafts, 89% (3%) versus 78% (2%), and postoperative functional class improved to a greater extent in IMA patients (87% of patients were in classes I and II). Arrhythmias and myocardial infarction were significant causes of late death only in patients with vein grafts. When patients are older than 70 years, patient selection factors clearly play an important role in the differential results between patients in whom the IMA is used and patients in whom vein grafts are used. As in younger patients, excellent results can be achieved in the elderly.

Long-term survival after postinfarction bypass operation: Early versus late operation

A study of 832 patients operated on within 30 days of infarction from 1974 to 1987 has resulted in 2,388 patient-years (maximum, 14 years) of prospectively acquired follow-up. This study excludes 74 patients in whom cardiogenic shock was the indication for operation. Five-year survival (+/- standard error) was 84% +/- 2%, 85% +/- 1%, and 90% +/- 1%, and 10-year survival was 71% +/- 4%, 68% +/- 1%, and 78% +/- 1% for patients with acute infarction, remote infarction, and no previous infarction, respectively. Age and left ventricular end-diastolic pressure significantly affected long-term survival for patients with acute infarction by both univariate and multivariate analysis. For patients aged less than 65 years, the 5-year and 10-year actuarial survival rates were 89% +/- 2% and 80% +/- 4%, compared with 75% +/- 3% and 58% +/- 9%, respectively, for patients aged more than 65 years. The survival percentages were 89% +/- 2% and 75% +/- 6% for patients with left ventricular end-diastolic pressure less than 15 mm Hg compared with 77% +/- 5% and 67% +/- 7% for patients with left ventricular end-diastolic pressure greater than 15 mm Hg. Operative mortality was 7.6% for patients operated on within 24 hours, compared with 4.1% for patients operated on between 2 and 30 days after infarction. Ten-year survival was similar (about 70%) for all timing groups. Based on these long-term results, there appears to be little to gain by delaying coronary artery bypass grafting, when indicated, after infarction occurs.

An unusual complication of cardiac transplantation—Infected aortic pseudoaneurysm

Infections after cardiac transplantation are a frequent cause of early morbidity and mortality. An unusual site for such a complication is at the aortic anastomotic suture line. We report a case of an infected aortic pseudoaneurysm, seen as recurrent septicemia, during the first 6 months after cardiac transplantation.

Hypoxic preconditioning in coronary microarteries: role of EDHF and K+ channel openers

BACKGROUND Hypoxic preconditioning may provide a useful method of myocardial protection in cardiac operations. The present study was designed to investigate the possible mechanisms of preconditioning regarding endothelium-derived hyperpolarizing factor (EDHF) and the effect of a potassium channel opener KRN4884 on the porcine coronary microartery in mimicking hypoxic preconditioning. METHODS Porcine coronary microartery rings (diameter 200 to 500 microm) studied in a myograph were divided into seven groups: (1) control group; (2) hypoxia-reoxygenation group (hypoxia for 60 minutes followed by reoxygenation for 30 minutes); (3) preconditioning group (hypoxia for 5 minutes followed by reoxygenation for 10 minutes before hypoxia reoxygenation); (4) KRN4884 pretreatment group (KRN4884 was added into the myograph chamber 20 minutes before hypoxia reoxygenation); (5) 5-hydroxydecanoate + KRN group (5-hydroxydecanoate was given 20 minutes before KRN4884 pretreatetment); (6) glibenclamide (GBC) + KRN group (GBC was added 20 minutes before KRN4884 pretreatment); and (7) endothelium denuded group (the endothelium was removed). The endothelium-derived hyperpolarizing factor-mediated relaxation to bradykinin was studied in the rings precontracted with U46619 in the presence of N(omega)-nitro-L-arginine and indomethacin. RESULTS The maximal relaxation induced by bradykinin was reduced in hypoxia reoxygenation (40.7% +/- 2.8% vs 66.9% +/- 2.5% in control, p = 0.000). This reduced relaxation was recovered in either preconditioning (64.6% +/- 4.6%, p = 0.002), or KRN4884 pretreatment (67.1% +/- 3.6%, p = 0.000). The 5-hydroxydecanoate, but not GBC pretreatment abolished the effect of KRN44884 pretreatment (67.1% +/- 3.6% vs 42.9% +/- 3%, p = 0.001). CONCLUSIONS Hypoxia reoxygenation reduces the relaxation mediated by endothelium-derived hyperpolarizing factor in the coronary microartery. This function can be restored by either hypoxic preconditioning or the K(ATP) channel opener KRN4884, and therefore K(ATP) channel openers may provide similar effect as preconditioning. The mechanism is mainly related to the mitochondrial ATP-sensitive K+ channels.

Mitral insufficiency after pericardiectomy for constrictive pericarditis

We report the case of a 24-year-old man in whom a clinical syndrome developed while he was on active military duty in Saudi Arabia that was subsequently diagnosed as constrictive pericarditis. Phrenic nerve to phrenic nerve pericardiectomy and posterior pericardial release successfully relieved the ventricular constriction with a resultant increase in the cardiac index from 1.9 to 3.8 L.min-1.m-2. Transesophageal echocardiographic monitoring during the operation disclosed trace mitral regurgitation before median sternotomy. The severity of the regurgitation noticeably increased to the moderate level immediately after pericardial resection. This echocardiographic finding had improved 1 week later, but the regurgitation still was greater than baseline. Mitral valve function had returned to baseline by 4 weeks after the operation. Possible mechanisms of this evolving pattern of perioperative mitral valve dysfunction are discussed.

Initial clinical trial of substernal epicardial echocardiography: SEEing a new window to the postoperative heart.

BACKGROUND Postoperative echocardiography windows are often of poor quality because of intervening air spaces around the heart and great vessels. We assessed the utility of a new commercially available adult chest drainage tube that has been modified with the addition of a sterile sleeve to accommodate the introduction of a nonsterile pediatric transesophageal echocardiography (TEE) probe. The TEE probe lies in a substernal epicardial position on the postoperative heart allowing one to perform substernal epicardial echocardiography (SEE). METHODS Informed consent was obtained from 21 consecutive adult cardiac operation patients. At the completion of the operation the SEE drainage tube was inserted through the rectus muscle and into the pericardium. After chest closure, all patients underwent a full echo examination using an Acuson pediatric biplane probe in the SEE position. Views obtained and ease of insertion were judged on a 1 to 10 (worst to best) scale. RESULTS Full SEE examinations were completed in an average of 12 minutes. Ease of probe entry and manipulation was excellent (ratings of 9.3 and 9.6, respectively). The quality of the anatomic images was also excellent. Substernal epicardial echocardiography tube positioning was integral to the orientation of the images obtained. There were no complications related to the placement of the SEE tubes or TEE probes. In 4 of 21 patients (19%) the SEE methodology was used serially in the intensive care unit to accurately assess ventricular function and filling during weaning of an intraaortic balloon and inotropic agents. CONCLUSIONS Substernal epicardial echocardiography is a safe and highly effective methodology for the serial echocardiographic assessment of the postoperative heart.

Mediastinal Hamartoma: Rare Presentation

Hamartomas are benign mesenchymal tumors that occur most commonly within lung parenchyma. A rare case of mediastinal hamartoma in a 76-year-old man is described. The patient underwent successful excision of the 9.5 × 10.5 × 8-cm mass.