Vasoactive role for angiotensin II type 2 receptors in human radial artery.

Angotensin II type 2 receptors are believed to counter the effects of the angiotensin type 1 receptors and there is no data relating to the co-localisation of either receptor in human diseased arteries. We sought to determine whether AT2R counter the effects of AT1R and immunolocalise both receptors to cells in human diseased arteries. Human radial arteries (RA, n=11) were placed in organ bath chambers and preincubated with the AT2R antagonist PD123319 for twenty minutes before an angiotensin II dose response curve. Immunohistochemistry was performed to identify receptors and pathology was quantified by image analysis software. We observed both receptors in human arteries. Angiogenic blood vessels within occluded arteries expressed both receptors. PD123319 impaired angiotensin II mediated vasoconstriction by 20 percent (n=5, p less than 0.05), however in other arteries, PD123319 exacerbated angiotensin II-mediated vasoconstriction by 60 percent (n=6, p less than 0.01), respectively. We conclude that inhibition of AT2R can enhance or reduce angiotensin II-mediated vasoconstriction. These data indicate that the role of AT2R in human diseased arteries is divergent although the AT2R-mediated vasorelaxation prevails.

Total arterial coronary artery bypass grafting in patients with diabetes: an 8-year experience.

OBJECTIVE: Coronary artery bypass grafting using arterial conduits may improve survival and minimise harvest site complications. However, in diabetes, the outcomes of coronary artery bypass grafting performed exclusively using arterial conduits are uncertain. We reviewed our experience with this approach. METHODS: From 1996 to 2008, 400 patients with diabetes (managed with oral hypoglycaemics, insulin or both) underwent primary isolated coronary artery bypass grafting for triple vessel coronary disease. In 246 (61.5%), total arterial revascularisation was achieved using single or bilateral internal thoracic arteries supplemented by one or more radial arteries (arterial group), while in the remaining 154 (38.5%), at least one venous conduit was used (mixed conduits group: mean 1.5 veins per patient). Propensity-score matching was used to adjust for bias. RESULTS: Total arterial revascularisation patients were more likely to be younger (arterial: 63 ± 10 years vs mixed: 67 ± 10 years, P < 0.0001), of elective priority (85% vs 75%, P = 0.018) and less likely to have moderate-severe left ventricular dysfunction (23% vs 36%, P = 0.024). Use of bilateral internal thoracic arteries was similar between groups (16% vs 11%, P = 0.19). There was a comparable in-hospital mortality (1.9% vs 2.0%, P > 0.99) and major morbidities, except the arterial group who experienced less stroke (0.4% vs 3.2% vs P = 0.04) and harvest site infections (0.4% vs 4%, P = 0.016). Mean follow was 7.8 ± 3.7 years. Estimated survival at 12-year survival in the arterial group was 80% ± 3.2% vs 54% ± 5.5% (P < 0.0001). Subsequently, 103 propensity-score-matched patient pairs were created between the two groups. After matching, in-hospital mortality (1% vs 2%, P > 0.99) and major morbidities were similar, as was an estimated 12-year survival (69% ± 6.1% vs 59% ± 6.5%, P > 0.99). CONCLUSIONS: The use of veins to supplement arterial conduits did not deleteriously affect survival. However, the significant number of patients receiving arterial grafts in both groups may have masked any potential difference. Greater numbers and longer follow-up will reveal the potential of this approach.

Calcitonin receptor immunoreactivity associated with specific cell types in diseased radial and internal mammary arteries.

AIMS: To determine and quantify calcitonin receptor (CTR) immunoreactivity associated with specific cell types within, and associated with, the endothelial layers, neo-intima, media and vasa vasorum of diseased radial and internal mammary arteries. METHODS AND RESULTS: Immunohistochemistry and anti-CTR antibodies were used to identify positive cells within remnants of diseased human radial (n = 3) and internal mammary arteries (n = 4) that remained after bypass surgery. Three cell types expressed CTR, including endothelial cells, fibroblast-like cells within the neo-intima, and cellular structures aligned with the smooth muscle cells of the media. Other smaller cells within the surrounding parenchyma of the vasa vasorum of diseased vessels and blood-borne cells were also immunoreactive. Immunoquantification of CTR expression (Intensity x Proportional Area) in the endothelium (P < 0.05), neo-intima (P < 0.02) and media (P < 0.03) established a significant statistical correlation (Students' two-tailed t-test) with the ratio of intimal/media thickness. CONCLUSIONS: Increased immunoreactivity developed using anti-CTR antibodies was associated with specific cell types in the endothelial layers, neo-intima, media and vasa vasorum of diseased regions of radial and internal mammary arteries, in which there was an increased intimal/media ratio. Furthermore, CTR+, blood-borne cells present in the vessels of diseased regions suggest recruitment into these surrounding tissues.

ACE2 and AT4R are present in diseased human blood vessels.

A growing body of evidence suggests that the angiotensin II fragments, Ang(1-7) and Ang(3-8), have a vasoactive role, however ACE2, the enzyme that produces Ang(1-7), or AT4R, the receptor that binds Ang (3-8), have yet been simultaneously localised in both normal and diseased human conduit blood vessels. We sought to determine the immunohistochemical distribution of ACE2 and the AT4R in human internal mammary and radial arteries from patients undergoing coronary artery bypass surgery. We found that ACE2 positive cells were abundant in both normal and diseased vessels, being present in neo-intima and in media. ACE2 positive immunoreactivity was not present in the endothelial layer of the conduit vessels, but was clearly evident in small newly formed angiogenic vessels as well as the vaso vasorum. Endothelial AT4R immunoreactivity were rarely observed in either normal and diseased arteries, but AT4R positive cells were observed adjacent to the internal elastic lamine in the internal mammary artery, in the neo-intima of radial arteries, as well as in the media of both internal mammary artery and radial artery. AT4R was abundant in vaso vasorum and within small angiogenic vessels. Both AT4R and ACE2 co-localised with smooth muscle cell alpha actin. This study identifies smooth muscle cell alpha actin positive ACE2 and AT4R in human blood vessels as well as in angiogenic vessels, indicating a possible role for these enzymes in pathological disease.

What factors influence the results of coronary artery bypass grafting in aged patients?

AIM: Early and late results were studied in order to improve the indication for coronary artery bypass grafting (CABG) and to enhance METHODS: A total of 1 973 patients aged 70 years and older who had undergone isolated CABG were studied. Elective operations (EL) were performed in 1 716 patients and 257 patients underwent urgent or emergency operations (UR/EM). Patients were divided into two groups; 104 patients aged 80 years and older (Oct. Group) and 1 869 patients of septuagenarians (Sept. Group). There were no differences between the groups in the number of diseased vessels. RESULTS: Total operative mortality rates in the Oct. and the Sept. groups were 7% and 4%, respectively. The operative mortality of elective surgery was 4% in both groups. The operative mortality of UR/EM CABG was significantly higher in the Oct. group than in the Sept. group (21% vs 6%). Operative mortality was significantly higher in patients with preoperative poor (<49%) left ventricular ejection fraction (LVEF) than in patients with higher (>50%) LVEF (6% vs 3%). Among preoperative risk factors, diabetes mellitus and peripheral vascular disease were significant contributory factors to operative death. In the follow-up study, 70% patients of the Oct. group and 72% patients of the Sept. group survived. Preoperative number of diseased vessels and number of CABG grafts did not influence the early and late CONCLUSION: Preoperative poor LVEF, diabetes mellitus and peripheral vascular disease were significant contributory factors to operative death. When feasible, CABG in octogenarians should be performed electively.

Prediction and functional analysis of native disorder in proteins from the three kingdoms of life.

An automatic method for recognizing natively disordered regions from amino acid sequence is described and benchmarked against predictors that were assessed at the latest critical assessment of techniques for protein structure prediction (CASP) experiment. The method attains a Wilcoxon score of 90.0, which represents a statistically significant improvement on the methods evaluated on the same targets at CASP. The classifier, DISOPRED2, was used to estimate the frequency of native disorder in several representative genomes from the three kingdoms of life. Putative, long (>30 residue) disordered segments are found to occur in 2.0% of archaean, 4.2% of eubacterial and 33.0% of eukaryotic proteins. The function of proteins with long predicted regions of disorder was investigated using the gene ontology annotations supplied with the Saccharomyces genome database. The analysis of the yeast proteome suggests that proteins containing disorder are often located in the cell nucleus and are involved in the regulation of transcription and cell signalling. The results also indicate that native disorder is associated with the molecular functions of kinase activity and nucleic acid binding.

Increased apoptosis in the heart of genetic hypertension, associated with increased fibroblasts.

OBJECTIVE: The present studies were undertaken to identify apoptosis in cardiomyocytes of genetic hypertension and to study the relationship among apoptosis, aging and blood pressure, and the effect of angiotensin-converting enzyme (ACE) inhibitors on apoptosis. METHODS: Apoptosis in the hearts of spontaneously hypertensive rats (SHR) was identified by electron microscopy (EM) and DNA laddering, and quantified from age 3 weeks to 64 weeks in comparison with normotensive rats (WKY). Fibroblasts and protein products of Bcl-2 and Bax were measured by quantitative immunohistochemistry. SHR were treated with ramipril, an ACE inhibitor. RESULTS: The results showed that: (1) ultrastructural characteristics of apoptosis were observed in cardiomyocytes of SHR, with shrinkage of the cell and condensation of the cytoplasm and chromatin. A DNA ladder was shown; (2) a significant increase in apoptosis in SHR began as early as age 4 weeks and reached a plateau at 16 weeks and maintained at high levels up to 64 weeks. Blood pressure (BP) in SHR started to increase significantly at age 5 weeks; (3) fibroblasts were significantly increased in the heart of SHR; (4) the ratio of Bcl-2/Bax was significantly reduced in SHR; and (6) ramipril effectively reduced apoptosis and fibroblasts, and increased the ratio of Bcl-2/Bax. CONCLUSION: Apoptosis occurs in the cardiomyocytes of genetic hypertension although fibroblasts are increased, and a significant, age-dependent increase in apoptosis is observed. The increase in apoptosis occurs before the difference in blood pressure is detectable. The ACE inhibitor ramipril may be useful for prevention of apoptosis in the heart.

Autologous neutrophil derived supernatants inhibit endothelium dependent relaxation in human coronary bypass graft.

OBJECTIVE: Spasm of internal mammary artery is a problem during coronary artery bypass grafting. The mechanism is unknown. The aim of this study was to determine whether supernatants derived from neutrophils affected endothelium dependent relaxation of human internal mammary artery. METHODS: The studies involved use of an organ chamber, measurement of cytosolic Ca2+, electron microscopy, and chemical characterisation. RESULTS: Autologous neutrophils and internal mammary artery were obtained from patients undergoing the bypass grafting. Supernatants derived from the neutrophils were used to treat the patients' internal mammary artery rings. The results showed that the supernatants derived from 1 x 10(3)-5 x 10(6) cells.ml-1 neutrophils produced a potent concentration dependent inhibition of the endothelium dependent relaxation to ATP, acetylcholine, and the calcium ionophore A23187, but not the endothelium independent relaxation to sodium nitroprusside. In cultured human endothelial cells, the neutrophil derived supernatants induced an increase in cytosolic calcium ([Ca2+]i), caused calcium oscillations, and desensitised the ATP induced increase in [Ca2+]i. The increased [Ca2+]i resulted from a calcium influx. The supernatants also induced an increase in vesicle formation and possibly exocytosis in the internal mammary artery endothelium. Chemical characterisation showed that the effect of the supernatants was caused by a factor that is stable to heat, extreme pH and protease, is negatively charged and weakly hydrophobic, and has a molecular weight under 500 Dalton. CONCLUSIONS: Autologous neutrophils release a stable non-protein small molecule that disturbs internal mammary artery endothelial function. Since it raises [Ca2+]i and causes possible exocytosis, it may have functions beyond its inhibition of vascular relaxation. This factor could be one of the contributors to internal mammary artery spasm and late atherosclerosis.

Reduction of endothelin levels by the dihydropyridine calcium antagonist nisoldipine and a 'natural factor' in cultured human endothelial cells.

OBJECTIVE: Endothelin is thought to be related to cardiovascular disease. The purpose of this study was to determine whether endothelin levels could be reduced by a calcium antagonist and a 'natural factor'. DESIGN: Since calcium ionophores can induce endothelin-1 messenger RNA synthesis in cultured endothelial cells, the calcium antagonist nisoldipine was used in this study to determine whether it could reduce endothelin levels. It has been reported that coculture of endothelial cells and smooth muscle cells from different species and different parts of the body can reduce endothelin levels. This study was also designed to determine whether coculture of the two cell types from the same species and the same section of an artery could reduce endothelin levels. METHODS: Cultured endothelial cells from human umbilical artery (HUAEC) and umbilical vein (HUVEC) were treated with increasing concentrations of nisoldipine. HUAEC were cocultured with human umbilical artery smooth muscle cells (HUASMC). Endothelin levels were measured by a radioimmunoassay. RESULTS: Incubation of the HUAEC with nisoldipine for either 7 or 24 h resulted in a dose-dependent (10(-8)-10(-5) mol/l) reduction in endothelin levels in the conditioned media. Endothelin levels in cell lysates were not detectable in either the absence or the presence of nisoldipine. This suggests that the reduction of endothelin levels in the media could be due to inhibition of endothelin synthesis. Under the same conditions, incubation of HUVEC with the same concentrations of nisoldipine produced a similar concentration-dependent reduction in endothelin levels. Endothelin levels were undetectable in the conditioned media from HUASMC. Coculture of HUAEC with HUASMC significantly reduced endothelin levels (P < 0.01) compared with HUAEC cultured alone. CONCLUSIONS: Endothelin levels can be reduced by the calcium antagonist nisoldipine and a 'natural factor' associated with smooth muscle cells.

Characterization and autoradiographic localization of beta-adrenoceptor subtypes in human cardiac tissues.

1 Receptor autoradiography using (-)-[125I]-cyanopindolol (CYP) was used to study the distribution of beta-adrenoceptor subtypes in human right atrial appendage, left atrial free wall, left ventricular papillary muscle and pericardium. 2 The binding of (-)-[125I]-CYP to slide-mounted tissue sections of human right atrial appendage was time-dependent (K1 = 4.11 +/- 1.01 X 10(8) M-1 min-1, K-1 = 1.47 +/- 0.25 X 10(-3) min-1, n = 3), saturable (42.02 +/- 2.96 pM, n = 4) and stereoselective with respect to the optical isomers of propranolol (pKD (-):8.97 +/- 0.02, (+):6.88 +/- 0.06, n = 3). 3 The proportions of beta-adrenoceptor subtypes were determined in slide-mounted tissue sections using the antagonists CGP 20712A (beta 1-selective) and ICI 118,551 (beta 2-selective). In right atrial appendage and left ventricular papillary muscle 40% (34-45%) of the beta-adrenoceptors were of the beta 2-subtype. 4 Images from X-ray film and nuclear emulsion coated coverslips exposed to (-)-[125I]-CYP-labelled sections showed an even distribution of beta-adrenoceptor subtypes over the myocardium of the right atrial appendage, left ventricular papillary muscle and left atrial free wall. Sections of pericardium exhibited predominantly beta 2-adrenoceptors. beta 2-Adrenoceptors were localized to the intimal surface of coronary arteries. 5 The selective beta 1-adrenoceptor agonist RO363 and beta 2-selective agonist procaterol produced concentration-dependent inotropic responses in right atrial appendage strips. Responses to RO363 were antagonized by CGP 20712A (pKB = 9.29) suggesting an interaction with beta 1-adrenoceptors. Responses to procaterol were antagonized by ICI 118,551 (pKB = 9.06) suggesting an interaction at beta 2-adrenoceptors. 6 The finding that a significant proportion of human myocardial adrenoceptors are of the beta 2-subtype has important clinical implications for the involvement of these receptors in the control of heart rate and force, and the autoradiographic evidence suggests other roles in the coronary vasculature and pericardium.

Autoradiographic localization and function of beta-adrenoceptors on the human internal mammary artery and saphenous vein.

1. Receptor autoradiography with (-)-[125I]-cyanopindolol (CYP) was used to study the distribution of beta 1- and beta 2-adrenoceptor subtypes in the human internal mammary artery and saphenous vein. 2. Images from X-ray film and nuclear emulsion coated coverslips, exposed to [125I]-CYP labelled sections, showed a high density of beta 2-adrenoceptors localized to the endothelium of the internal mammary artery and fewer beta 2-adrenoceptors on the smooth muscle. 3. The function of beta-adrenoceptors in ring preparations of the internal mammary artery was investigated in organ bath studies. (-)-Isoprenaline produced concentration-dependent relaxation of phenylephrine contracted rings. The potency and maximal effects of (-)-isoprenaline were not influenced by the presence of the endothelium. 4. Images of [125I]-CYP binding to the saphenous vein, from X-ray film and nuclear emulsion coated coverslips, showed localization of beta 2-adrenoceptors to the outer smooth muscle and not to the endothelium. 5. Relaxation of mammary artery and saphenous vein to (-)-isoprenaline is mediated via beta 2-adrenoceptors located on the smooth muscle. Endothelial beta 2-adrenoceptors, although present on the internal mammary artery, mediate other functions.

Tolerance to glyceryl trinitrate in isolated human internal mammary arteries.

The purpose of this study was to examine the vascular reactivity of segments of internal mammary artery removed from patients undergoing coronary artery bypass operations. Responses to relaxant and contractile agents were compared in arteries removed from patients who had or had not been treated with glyceryl trinitrate after admission to the hospital until operation. Segments of mammary artery were removed from 13 patients who underwent coronary artery bypass grafting. Endothelium-containing rings of artery, 3 to 5 mm long, were suspended in physiologic saline solution in 20 ml organ baths. Responses to the endothelium-dependent relaxant acetylcholine and the endothelium-independent relaxants glyceryl trinitrate and sodium nitroprusside were compared. In addition, contractile responses to phenylephrine and 9,11-dideoxy-9 alpha,11 alpha-methanoepoxy prostaglandin F2 alpha (U46619) were examined. Glyceryl trinitrate-induced relaxation was significantly impaired in mammary artery segments from patients treated with that nitrate before operation; the responses to acetylcholine and sodium nitroprusside were not affected. Previous treatment with glyceryl trinitrate also reduced the contractile responses to both phenylephrine and U46619. These studies indicate that treatment of patients with glyceryl trinitrate before operation induces significant tolerance to this agent in the mammary artery; however, there was no evidence of cross tolerance to sodium nitroprusside or the endothelium-dependent vasodilator acetylcholine. Glyceryl trinitrate may therefore not always be effective in dilating mammary artery grafts and sodium nitroprusside may be a more effective dilator of the internal mammary artery in patients who have been treated with glyceryl trinitrate before operation.

Surgical implications of variations in hand collateral circulation: anatomy revisited.

OBJECTIVES: One of the risks associated with harvesting the radial artery is hand ischemia. Accordingly, this study investigated the variations of the hand collateral circulation. METHODS: Fifty hands of cadavers were examined. Variations of the palmar arches were recorded. A classic superficial palmar arch was defined as direct continuity between the ulnar artery and the superficial palmar branch of the radial artery. A classic complete deep palmar arch was defined as direct continuity between the radial artery and the deep branch of the ulnar artery. RESULTS: A classic superficial palmar arch was found in 10% (5/50) of hands, and a classic complete deep palmar arch was found in 90% (45/50) of hands. The superficial palmar branch of the ulnar artery supplied blood to all fingers in 66% (33/50) of hands. Although the superficial palmar branch of the ulnar artery was continuous with the radial artery in only 34% (17/50) of hands (including the classic type of superficial palmar arch), every hand had at least one major branch connecting the radial and ulnar arteries. CONCLUSIONS: Variations in the terminations of the radial and ulnar arteries are common. Although the classic type of superficial palmar arch occurs relatively infrequently, there is always a significant anastomosis between the radial and the ulnar artery in the hand. This anatomic study confirms the presence of a collateral supply in the hand. In the absence of vascular disease, harvesting the radial artery should be regarded as a safe procedure.

Left ventricular aneurysm repair in rats: structural, functional, and molecular consequences.

OBJECTIVES: This study examined the effects of aneurysm repair in a rat model of myocardial infarction on functional indices and on the spatiotemporal distribution of cardiac contractile protein and natriuretic peptide messenger RNA. METHODS: In a rat infarct model, expanded left ventricular aneurysms were plicated 4 weeks after infarction. At 30 weeks, transverse heart sections were taken at 4 levels (apex [level 1] through base [level 4]) and assessed by in situ hybridization histochemistry to determine regional messenger RNA levels of pre-pro-atrial natriuretic peptide, cardiac alpha-actin, skeletal alpha-actin, myosin light chain-2v, and beta-myosin heavy chain. RESULTS: Rats with plicated left ventricular aneurysms had reduced left ventricular endocardial circumference (19%, P <.005), lower heart weight ratio (31%, P <.05), left ventricular end-diastolic pressures (51%, P <.05), and increased +/-dP/dt (34%-38%, P <.05). Cardiac messenger RNA levels of pre-pro-atrial natriuretic peptide were reduced in the septum (levels 2 and 3), and skeletal alpha-actin levels were reduced in the septum and left ventricular free wall of plicated rats (level 3). beta-Myosin heavy chain levels were markedly reduced in peri-infarct regions of the left ventricular free wall, septum, and right ventricle in plicated rats at level 4, whereas myosin light chain-2v levels were reduced at levels 2 and 4 in the left ventricular free wall and at level 4 in the right ventricle. CONCLUSIONS: Plication of left ventricular aneurysm after infarction in the rat significantly reduced cardiac hypertrophy, improved cardiac function, and reduced the upregulation of pre-pro-atrial natriuretic peptide and both fetal and adult contractile protein isoforms associated with cardiac hypertrophy.

Preoperative assessment of hand circulation by means of Doppler ultrasonography and the modified Allen test.

OBJECTIVE: The aims of this study were as follows: (1) to evaluate Doppler ultrasonography in assessing hand collateral circulation; (2) to define the criteria for an abnormal Doppler ultrasonography dynamic test result; and (3) to validate the modified Allen test. METHODS: The hand circulation of 71 patients scheduled for coronary artery bypass grafting was assessed by means of the Allen test and Doppler ultrasonography. The flow in the superficial palmar branch of the radial artery, the ulnar artery, and the dorsal digital thumb artery with and without radial artery compression were recorded. Flow patterns in the superficial palmar branch of the radial artery, the ulnar artery, and the dorsal digital thumb artery with radial artery compression were categorized into 4 groups: (1) no flow; (2) decreased flow; (3) reversed flow; and (4) increased flow. RESULTS: Among the 71 hands, 4 (5.6%) had an abnormal Allen test result (>10 seconds). Seven (10.6%) of 66 superficial palmar branches of the radial artery, 3 (4.2%) of 71 ulnar arteries, and 2 (2.8%) of 71 dorsal digital thumb arteries showed no flow with radial artery compression, as measured by Doppler ultrasonography. There were significant differences among the 4 groups (superficial palmar branch of the radial artery: F = 7.0, P <.001; ulnar artery: F = 13.1, P <.001; and dorsal digital thumb artery: F = 8.4, P <.001) for the Allen test. Pairwise comparisons showed that when subjected to an Allen test, category 1 patients (no flow) had significantly longer recovery times compared with the other groups (P <.02 in all cases) for the superficial palmar branch of the radial artery, the ulnar artery, and the dorsal digital thumb artery. CONCLUSION: Absence of flow in the dorsal digital thumb artery with radial artery compression is considered an absolute contraindication to radial artery harvesting. An increased recovery time with the modified Allen test predicts absence of flow in the dorsal digital thumb artery in Doppler ultrasonographic flow patterns. This demonstrates the validity of the modified Allen test for primary screening.

Direct vasodilator effect of milrinone, an inotropic drug, on arterial coronary bypass grafts. FANZCA .

Milrinone is an inotropic drug with vasodilator activity that has been shown to be useful in increasing cardiac output and decreasing wedge pressure. Despite these advantages, it is unknown whether this drug can be used for the treatment of perioperative spasm of coronary bypass grafts. This study was undertaken to investigate the in vitro vascular effect of milrinone on internal thoracic arteries obtained from patients undergoing coronary artery bypass grafting. The results showed that milrinone produced a potent, concentration-dependent, preventive effect on the norepinephrine-induced contraction of internal thoracic arteries, as well as reversing contraction of internal thoracic arteries by receptor-dependent agents, including the thromboxane A2 mimetic U46619, the vasoconstrictor peptide endothelin-1, and the alpha1-adrenal receptor agonist phenylephrine. The relaxing effect of milrinone was weaker, however, on internal thoracic arteries contracted with 25 mmol/L potassium chloride. Comparison of milrinone with other vasodilators, including papaverine, nitroprusside, and glyceryl trinitrate, showed milrinone to be more potent than papaverine but less potent than nitroprusside and glyceryl trinitrate. The inhibitory effect of milrinone on internal thoracic artery contraction appeared as a reduction in contractile force, not as an increase in the values of concentrations of the agonists causing 50% maximal contraction, which indicates that milrinone exerts its vasodilator effect directly on the smooth muscles, not on the membrane receptors. The results also showed no significant difference in relaxing effect between internal thoracic artery rings with and without endothelium. In conclusion, this study provides experimental evidence that milrinone is a potent, endothelium-independent, direct vasodilator of the human internal thoracic artery and provides the scientific rationale for a future clinical trial with this drug for the perioperative treatment of internal thoracic artery spasm in cardiac surgical patients.

Pharmacologic dilatation of the internal mammary artery during coronary bypass grafting.

Spasm of the internal mammary artery during coronary bypass grafting is a widely recognized problem during and after mobilization of the IMA. On the basis of previous laboratory studies, we have developed a buffered vasodilator solution containing glyceryl trinitrate and verapamil (pH 7.4). When tested in human internal mammary artery segments in the organ bath, this solution caused full relaxation of the segments with a 1- to 2-minute onset and a duration of action of more than 2 hours. In 31 patients undergoing internal mammary artery grafting, flow through the internal mammary artery was measured immediately after mobilization and 20 minutes later. In 10 untreated patients, flow increased by 13% from 41.8 +/- 7.1 to 47.3 +/- 7.5 ml/min (p < 0.025). In 11 patients, intraluminal injection of glyceryl trinitrate-verapamil solution into the internal mammary artery on one side caused an increase in flow of 55 +/- 10 ml/min (95%), which was greater than that caused by Ringer's solution, 22 +/- 8 ml/min (53%), in the opposite internal mammary artery (p < 0.025). In another 10 patients intraluminal injection of glyceryl trinitrate-verapamil solution in one internal mammary artery caused an increase in flow of 57.9 +/- 8.7 ml/min (107%), which was similar to that caused by papaverine solution (pH 5.2) in the opposite internal mammary artery of 45.0 +/- 12.3 ml/min (80%). We conclude that intraluminal injection of vasodilator solution is effective in dilating the IMA graft and that because of its rapid onset, long action, and neutral pH, glyceryl trinitrate-verapamil solution may be preferable to papaverine.

Retrograde vital organ perfusion during aortic arch repair.

A technique is described for cerebral and other vital organ preservation during aortic arch repair using retrograde venous perfusion at 20 degrees C. This technique retains the excellent operating conditions of deep hypothermia and circulatory arrest. Potential benefits include shortening of the cooling and rewarming time, reduction of coagulopathy, prevention of emboli, and extension of the safe period of antegrade circulatory arrest.

Anatomic and hemodynamic considerations influencing the efficiency of retrograde cardioplegia.

One of the major issues raised by cardiac surgical procedures requiring cardiopulmonary bypass is the question of myocardial protection. The preferred route for the administration of cardioplegia is controversial. A number of studies show the beneficial effects of retrograde cardioplegia but some demonstrate only partial or poor myocardial protection. This paper reviews the anatomy and anatomic variations of the coronary sinus, the coronary sinus orifice and cardiac veins, and the major systemic venous drainage, all of which may affect the distribution of retrograde cardioplegia.

Outcome of geometric endoventricular repair in impaired left ventricular function.

BACKGROUND: Traditionally, repair of left ventricular aneurysms has been limited to patients with large localized ventricular aneurysms. Repair of dyskinetic segments in the setting of poor left ventricular function is still contentious. METHODS: Forty patients underwent geometric endoventricular repair, a new technique of ventricular aneurysm repair, over a 2-year period. Two groups of patients undergoing coronary artery bypass grafting (CABG) for left ventricular dysfunction in the same time period were reviewed. Group 1 comprised 23 consecutive patients who underwent geometric endo-ventricular repair along with CABGs, whereas group II consisted of 22 patients who underwent CABG alone. RESULTS: The early mortality was 9.1% in group I (1 cardiac, 1 noncardiac) and 0 in group II (NS). New York Heart Association class was remarkably improved from 3.4 to 1.4 (p < 0.05) in group I and to a lesser extent in group II (3.7+/-0.5 versus 2.3+/-0.5). Diastolic dimension of left ventricle was significantly reduced from 5.6 cm to 4.4 cm (p < 0.05) in group I and virtually unchanged in group II. There was one late death in each of the groups. CONCLUSIONS: This technique of geometric left ventricular aneurysm repair is useful in patients with dyskinetic segments and may help in reducing cardiac size.