Assessment of internal thoracic artery vasoreactivity in response to sublingual nitroglycerin.

BACKGROUND: We have previously shown the feasibility of assessing internal thoracic artery (ITA) size and blood flow hemodynamics before and after coronary artery bypass grafting using color-flow duplex ultrasound. This noninvasive method would be an ideal diagnostic tool for the evaluation of ITA graft status after therapeutic interventions in a patient with angina after coronary artery bypass grafting. The purpose of this study was to investigate the effects of nitroglycerin on the diameter and blood flow velocities of the left native ITA before coronary artery bypass grafting and the ITA graft postoperatively. METHODS: The study consisted of 24 male patients (mean age, 59 +/- 2.3 years) who had undergone elective coronary artery bypass grafting using a left ITA graft to the left anterior descending artery, with additional saphenous vein grafts. Color-flow duplex ultrasound (5.0-MHz transducer) was used for both the preoperative imaging of native ITAs and the postoperative study of ITA grafts before patient discharge. Repeated-measures analysis of variance was used to compare measurements of the ITA size and flow velocities (peak systolic velocity and end-diastolic velocity) at 5, 10, and 15 minutes after a single dose of sublingual nitroglycerin (0.4 mg) with the baseline values obtained without nitroglycerin. RESULTS: The preoperative native left ITA and the postoperative left ITA graft diameters responded to sublingual nitroglycerin by showing a rapid and significant increase beginning at 5 minutes and lasting up to 15 minutes (p = 0.0001). Sublingual nitroglycerin caused the peak systolic velocity of the native left ITA to be augmented at 5 minutes (p = 0.0002), and this effect was still apparent at 10 minutes (p = 0.0001) and 15 minutes (p = 0.0192). However, postoperative left ITA graft peak systolic velocities remained unaffected by the sublingual nitroglycerin (p = not significant). CONCLUSIONS: We conclude that instantaneous noninvasive measurement of ITA graft size and blood flow velocities after a therapeutic drug intervention may be clinically useful, particularly in a post-coronary artery bypass grafting patient with recurrent angina.

Influence of increasing age on long-term survival after coronary artery bypass grafting.

BACKGROUND: Despite the steady increase in the number of elderly patients undergoing coronary artery bypass grafting (CABG), skepticism still exists as to whether this operation is justified in older people with a reduced life expectancy. The purpose of this study was to examine the effects of increasing age on outcome after CABG. METHODS: A retrospective chart review was performed on 1,689 consecutive veterans of the United States Armed Forces undergoing isolated primary CABG from January 1972 through December 1994. For better comparison, they were arbitrarily divided by age into three groups: group I, 50 years of age or less (n = 213), group II, between 51 and 70 years of age (n = 1,258), and group III, more than 70 years of age (n = 218). Long-term survival for each group was compared to that of their age-matched population derived from Wisconsin life tables. RESULTS: The preoperative ejection fraction was comparable in all three groups (p = 0.114). The patients older than 70 years of age had received more grafts per operation than the patients 50 years of age and younger (3.7 versus 3.3) (p = 0.0001). Although the aortic cross-clamp time was prolonged with advanced age (p = 0.0002), the cardiopulmonary perfusion time was shortest in elderly patients (p = 0.0001). The early (30-day) mortality for the entire study population was 1.3%. There was a linear correlation between increasing age and early (30-day) mortality: group I, 0.5% (1/213); group II, 1.0% (13/1,258); and group III, 3.2% (7/218). The overall 10-year actuarial survival for all patients was 67%. The 10-year survival was diminished with increasing age (p = 0.0001): 74% for group I, 68% for group II, and 47% for group III. Comparative analysis of the three groups with their age-matched counterparts demonstrated an age-related survival after CABG. In group I, reduced survival was evident 4 years after the CABG: the 10-year survival in group I was 74.2%, and the survival of their age-matched population was 93.4% (confidence interval, 67% to 81.9%). In group II a survival difference was obvious 8 years after CABG: 10-year survival of 67.5% versus 75.1% in their age-matched population (confidence interval, 64.8% to 71.6%). In the elderly group of patients, no survival difference was noted: 10-year survival of 42.7% versus 45.9% of the age-matched population (confidence interval, 29.8% to 64.6%). CONCLUSIONS: An acceptable early mortality and long-term survival equal to those seen for an age-matched elderly population are sound outcome measures that support the justification of CABG in older patients irrespective of age.

Neurogenic vasoreactivity of human internal thoracic artery is unaffected by endothelial cell integrity.

BACKGROUND: The role of internal thoracic artery (ITA) nervous supply has not been previously considered as a potential factor influencing excellent long-term patency of an ITA graft. To define the interaction between the primary afferent neurons and endothelial cells of ITA, we investigated the effects of acute capsaicin administration in vitro on the isometric tension of human ITAs. METHODS: Vessels were obtained from patients undergoing coronary bypass or from multi-organ transplant donors. Thirty-three ITA segments (5 mm wide) were suspended as rings between two stainless-steel stir-ups in water-jacketed (37 degrees C) tissue baths. The tissue baths contained 10 ml physiological salt solution (PSS) of the following composition (mM/L): NaCl 119, KCl 4.7, NaH2PO4 1.0, MgCl2 0.5, CaCl2 2.5, NaHCO3 25, and glucose 11, aerated continuously with 95% O2 and 5% CO2. Peptidase inhibitors, phosphoramidon (1 microM) and captopril (1 microM), were added to PSS to decrease peptide degradation. Mechanical responses were measured isometrically and recorded on a polygraph via isometric force transducers. Vessels were preconstricted with submaximal concentrations of norepinephrine. After the tension had stabilized, capsaicin was added cumulatively to the tissue bath. The viability of ITA was verified by its responses to endothelial-dependent (acetylcholine, 1 microM) (n=20) and endothelial-independent (sodium nitroprusside, 10 microM) (n=13) vasodilators. RESULTS: The exposure of capsaicin (3 microM) to human ITA produced varied effects on ITA irrespective of its endothelium. Capsaicin induced contraction of the ITA smooth muscle in 13 endothelium-intact ITA segments while it produced vasoconstriction in 9 endothelium-denuded ITAs (p=0.6437). In response to capsaicin, relaxation of ITA smooth muscle was observed in 7 ITA rings with endothelium, while vasodilation was present in 4 ITA segments without endothelium (p=0.4099). CONCLUSIONS: Capsaicin-sensitive neurons encircling human ITA produce a neurogenic vasoreactive response independent of ITA endothelial cell integrity.

The influence of cardiopulmonary function on outcome of veterans undergoing resectional therapy for lung cancer.

BACKGROUND: The unknown but presumably poor preoperative cardiopulmonary function of U.S. Armed Forces veterans with bronchogenic cancer may dissuade surgeons performing necessary major lung resection. The purpose of this study was to investigate the relationship between preoperative cardiopulmonary risk and the outcome of veterans undergoing pulmonary resection for bronchogenic carcinoma. METHODS: A retrospective chart review was performed on 79 veterans who underwent lung resection for bronchogenic cancer between March 1990 and June 1995. Preoperative cardiac function was assessed by 1) history of heart disease (myocardial infarction, previous open heart surgery, and hypertension), 2) electrocardiogram, EKG, and 3) transthoracic echocardiography, TTE (ejection fraction and left ventricular wall motion abnormalities). Pulmonary reserve was evaluated by 1) history of lung disease (active smoking, known chronic obstructive pulmonary disease, COPD), and 2) spirometry (forced expiratory volume in 1 second, FEV1, and minute ventilation volume, MVV). Resections were performed by standard pulmonary techniques and follow-up data was available in all patients. RESULTS: All patients were males except one, with a mean age of 66+/-1.0 yrs (range=32 to 81 yrs). Fifty-one patients (64.60%) had a history of COPD while one-third of the veterans were smoking and using excessive alcohol just prior to surgery. Twenty-four patients (29%) had abnormal preoperative EKG and only 10 (15%) had prior myocardial infarction. Eleven patients (13.9%) had undergone previous coronary bypass surgery. Average preoperative left ventricular ejection fraction was 63+/-2% (range=41 to 80%) and left ventricular wall motion abnormalities were present in only 6 patients (8%). Mean preoperative FEV1 was 2.2+/-0.1 L (range=0.6-4.1 L) and MW was 87+/-4 L/min (range=26-198 L/min). A lobectomy was performed in 68 patients (86.1%), pneumonectomy in 10 (12.7%), and wedge resection in 1 (1.2%). The most common types of cancer were squamous cell (36 patients) and adenocarcinoma (31 patients). While pulmonary complications (atelectasis, prolonged air leak, pneumonia) occurred in 8 patients (10%), only two (3%) suffered nonpulmonary complications (ischemic bowel disease). For all veterans with bronchogenic cancer, early (30-day) mortality after major lung resection was 3.9% (3/79): 1.5% (1/68) after lobectomy, and 20% (2/10) after pneumonectomy (p=not significant). Overall survival at 5 years was 39.5%. CONCLUSIONS: Preoperative cardiopulmonary risk for veterans with bronchogenic cancer is acceptable and lung resection can be performed with good outcomes in this distinct patient population.

Association of osteopontin with calcification in human mitral valves.

BACKGROUND: Little is known about the long-standing inflammation leading to calcification within heart valves. Osteopontin, a phosphorylated glycoprotein, is present within atheromatous calcific plagues in response to vascular endothelial injury. The purpose of the study was to investigate whether osteopontin exists in calcific mitral valve leaflets in human beings, and to determine a link between chronic inflammation leading to mitral stenosis and the osteopontin status of mitral valvular tissue. MATERIALS AND METHODS: We reviewed the case histories of 17 patients who underwent mitral valve replacement therapy for mitral stenosis between 1995 and 1997 (8 men and 9 women, mean age 61 years). Hybrid mouse monoclonal immunoglobulin G1 antibodies were used for immunohistochemical detection of osteopontin in the acetone-fixed specimen. The control group consisted of normal mitral valve tissue from cardiomyopathy patients who underwent cardiac transplantation. RESULTS: A weak osteopontin immunoreactivity was present in apparently normal mitral valve tissue obtained from cardiomyopathy patients. All mitral stenosis patients had immunoreactivity (17/17) for osteopontin within calcific deposits of mitral valve tissue. The intensity of osteopontin activity had a strong association with increasing macrophage and calcium aggregations in the mitral valvular tissue. We found no correlation between osteopontin status and clinical features on the prognosis of calcific mitral stenosis. CONCLUSIONS: We conclude that osteopontin coexists with intimal macrophages in calcific human mitral valve tissue. Demonstration of such association between the presence of osteopontin and calcification in human mitral valves is consistent with the hypothesis that calcification in this tissue is, at least in part, an actively mediated phenomenon.

Clinical importance of measuring coronary graft flows in the revascularized heart. Ultrasonic or electromagnetic?

BACKGROUND: In the past, routine coronary graft flow measurement at the end of coronary artery bypass grafting (CABG) was not universally adopted by cardiac surgeons due to the lack of reliable flow measurement techniques. The purpose of this study was to investigate the efficacy of ultrasonic and electromagnetic techniques in coronary graft flow measurements and to determine the relationship, if any, between intraoperative ultrasonic or electromagnetic coronary graft flows and postoperative early clinical outcome. METHODS: We studied 66 consecutive patients who underwent elective CABG using internal thoracic artery (ITA) and reversed saphenous vein graft (SVG) conduits. All patients were males with the mean age of 65 +/- 1 yrs (range = 45 to 80 yrs). Coronary bypass graft flows (both ITA and SVG) were determined by the use of both ultrasonic and electromagnetic flowmeters. In addition, the flow waveform pattern was continuously recorded and analyzed with the ultrasonic technique. In this prospective non-randomized study, the following variables were considered in the forward stepwise multivariate regression analysis of the data: age, weight, body surface area, ejection fraction, perfusion and ischemia times, number of grafts, amount of allogenic banked blood, platelets, fresh frozen plasma transfusions, cardiac output/index, ultrasonic (USF) and electromagnetic flows (EMF), length of intensive care unit (ICU) and hospital stays, and early (30-day) mortality. RESULTS: Based on their location, 226 grafts were divided into four groups: (I) ITA to left anterior descending (LAD) (n = 66) 34 +/- 2.5 ml/min USF and 45 +/- 4.4 ml/min EMF; (II) SVG to circumflex (CX) (n = 62) 33 +/- 2.4 m/min USF and 58 +/- 4.9 ml/min EMF; (III) SVG to diagonal (DIAG) (n = 37); 30 +/- 3.5 ml/min USF and 50 +/- 6.0 ml/min EMF; (IV) SVG to right coronary artery (RCA) (n = 61); 36 +/- 3.1 ml/min USF and 56 +/- 5.3 ml/min EMF. Electromagnetic flow measurements were higher than USF values in all locations (p < 0.05). Difficulties in obtaining proper contact with the vessel wall and finding suitable size probes were major drawbacks in measurement of ITA graft flow by the use of electromagnetic technique. All flow measurements were done within 10 minutes or less. There was no demonstrable correlation between the length of stay (ICU and hospital), and coronary graft flows at the ITA to LAD, SVG to DIAG, or SVG to CX locations. However, ultrasonic coronary graft flows at the SVG to RCA location had a significant inverse correlation with the length of ICU and hospital stays (r = -0.45, p < 0.0005 for both). Early mortality was unaffected by the intraoperative coronary graft flow values (p = NS). CONCLUSIONS: The ultrasonic flowmeter is well-suited for intraoperative assessment of arterial and venous coronary graft flows at the completion of CABG. There is a real potential for using intraoperative graft flow values to predict early outcome after coronary bypass.

Long-term survival benefit of internal thoracic artery grafting is negligible in a patient with bad ventricle.

BACKGROUND: Although the internal thoracic artery (ITA) graft is well known for its benefit of enhancing patient longevity after coronary artery bypass grafting (CABG), whether its superior patency is associated with improved patient survival at all levels of left ventricular function is unknown. The purpose of this study was to determine whether the use of ITA grafting during CABG confers improved survival benefit to patients with impaired preoperative left ventricular function. METHODS: A retrospective chart review was performed in 966 patients who had undergone isolated primary CABG between 1984 and 1995. The study population included 320 patients with only venous conduits (no-ITA group) and 646 patients with at least one ITA conduit (ITA group). A Cox partial likelihood approach was used to model the instantaneous mortality risk ratios as functions of ITA use and preoperative ejection fraction (EF). The forward stepwise regression model specifically examined the following potential confounders in the risk analyses: year of operation, patient age, weight, body surface area, graft location, number of grafts, perfusion time, ischemia time and Veterans Administration preoperative cardiac surgical risk estimates. RESULTS: Early (30-day) mortality in the ITA group (0.5%) was lower than the no-ITA group (4.1%) (p=0.0004). While 91% of the ITA group patients were still alive, only 70% of the no-ITA group patients were long-term survivors (p=0.0001). The ITA risk ratios for the increasing proportions of EF were not the same. In patients with E<0.40, the ITA risk ratio, 2.96, was significantly different (p=0.0001). It was only for EF >0.46, a significant survival benefit due to an ITA graft could be detected. The ITA-EF relationship was not confounded by the inclusion of those potential confounding variables in the model. CONCLUSIONS: Patient survival after CABG using an ITA graft may be affected by the level of preoperative EF. The internal thoracic artery-specific patient survival benefit appears to be less in a patient with poor left ventricular function.

Neurogenic vasoreactive response of human internal thoracic artery smooth muscle.

The interaction between primary afferent neurons containing neuropeptides and the vascular smooth muscle is incompletely understood. To explore the function of perivascular afferent neurons and to determine whether they produce local effects on vascular smooth muscle cells, we investigated the effects of acute capsaicin and substance P administration in vitro on human internal thoracic arteries (ITA). Vessels were obtained from patients undergoing coronary bypass or from multiorgan transplant donors. Fourteen ITA segments (5 mm wide) were suspended as rings between two stainless-steel stirrups in water-jacketed (37 degrees C) tissue baths under 2.5 to 3 g of basal tension. The tissue baths contained 10 mL physiological salt solution (PSS) of the following composition (mM): NaCl, 119; KCl, 4.7; NaH2PO4, 1.0; MgCl2, 0.5; CaCl2, 2.5; NaHCO3, 25; and glucose, 11; aerated continuously with 95% O2 and 5% CO2. Peptidase inhibitors (phosphoramidon and captopril) were added to PSS to decrease peptide degradation. Mechanical responses were measured isometrically and recorded on a polygraph via isotonic force transducers. Vessels were preconstricted with submaximal concentrations of norepinephrine. After the tension had stabilized, substance P or capsaicin was added cumulatively to the tissue bath. At the end of the experiments, the viability of ITA was verified by its responses to endothelial-dependent (acetylcholine) and endothelial-independent (sodium nitroprusside) vasodilators. In the endothelium-intact ITA segments, substance P produced relaxation of ITA smooth muscle while it induced slight contraction when the ITA was devoid of its endothelium (P = 0.0585). The addition of capsaicin to human ITA primarily produced contractile effects on the developed smooth muscle force. The capsaicin-induced contraction of the ITA smooth muscle was independent of endothelial cell integrity, although contraction was greater in the endothelium-intact ITA segments (P = 0.0165). The acute capsaicin exposure of human ITA revealed that primary afferent neurons containing neuropeptides innervate human ITAs. There is a real potential for perivascular afferent neurons and sensory peptides to influence the ITA smooth muscle function.

Lung lymph oncotic pressure may not modulate pulmonary vascular filtration in sheep.

We tested the hypothesis that plasma oncotic pressure alone, not the plasma-to-lymph oncotic pressure difference, modulates pulmonary transvascular fluid filtration. To do this we measured lung lymph flow after raising left atrial pressure (by inflating a balloon) in sheep that were receiving a continuous (32 h) infusion of dextran 40. For comparison, we also raised left atrial pressure elevation, plasma oncotic pressures in dextran and control sheep, respectively, were 39.5 +/- 4.5 and 17.7 +/- 2.2 mm Hg; plasma-to-lymph oncotic pressure gradients, respectively, were 4.4 +/- 0.6 and 4.4 +/- 0.6 mm Hg. Left atrial pressure elevation during dextran infusion increased lung lymph flow by a factor of 2.4 +/- 0.4, compared with a factor of 4.2 +/- 2.3 in control sheep. Thus, left atrial pressure elevation increased lymph flow less in dextran-treated animals than in control animals, even though the plasma-to-lymph oncotic pressure gradients were equal. This suggests that plasma oncotic pressure alone may be a more important determinant of pulmonary transvascular fluid filtration than the plasma-to-lymph oncotic pressure difference.

Filtration of diaspirin crosslinked hemoglobin into lung and soft tissue lymph.

Diaspirin crosslinked hemoglobin (DCHb) is a new blood substitute manufactured from human blood. To evaluate its microvascular filtration properties, we infused DCLHb into unanesthetized sheep (10%, 20 ml/kg) and measured the flow and composition of lung and soft tissue lymph. For comparison, we also infused human serum albumin (HSA; 10%, 20 ml/kg). DCLHb raised systemic and pulmonary arterial pressures from baseline values of 83 +/- 7 and 13 +/- 2 mm Hg, respectively, to peak values of 113 +/- 9 and 26 +/- 3 mm Hg (p < 0.05 versus baseline). These increases were significantly greater than those associated with HSA, which raised systemic and pulmonary arterial pressures from baseline values of 86 +/- 4 and 13 +/- 2 mm Hg, respectively, to peak values of 97 +/- 3 and 21 +/- 7 mm Hg (p <= 0.05 versus baseline and versus DCLHb). These differences reflect the known pressor properties of DCLHb. Accordingly, DCLHb raised lung and soft tissue lymph flows to peak values of 12.2 +/- 3.8 and 1.6 +/- 0.7 ml/30 min, respectively, while HSA raised lung and soft tissue lymph flows to peak values of 7.5 +/- 4.8 and 4.6 +/- 1.9 ml/30 min, respectively (p <= 0.05 versus DCLHb). The half-times of DCLHb equilibration from plasma into lung and soft tissue lymph of 1. 0 +/- 0.3 and 2.1 +/- 1.1 h, respectively, were significantly faster than HSA equilibration half-times of 3.1 +/- 0.2 and 3.8 +/- 0.9 h. Filtration differences between DCLHb and HSA appear to be due to the pressor properties DCLHb.