Kyung W. Park

The Direct Vasomotor Effect of Thyroid Hormones on Rat Skeletal Muscle Resistance Arteries

The present study examines the hypothesis that the hormones have direct vasodilatory effects and attempts to determine whether the effects are endothelium-dependent. Rat skeletal muscle resistance arteries of approximately 100 micro m were dissected, and vessel diameter changes were monitored using a videodetection system. After equilibration at 37[degree sign]C, each vessel was preconstricted with the thromboxane analog U46619 1 micro M, and the percentage of dilation was measured after exposure to increasing concentrations of triiodothyronine (T3) or levothyroxine (T4) (10-10 to 10-7 M). Dilation in response to T3 was also measured after endothelial denudation and pretreatment with the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA) 10 micro M, the cyclooxygenase inhibitor indomethacin 10 micro M, the adenosine triphosphate-sensitive K+ channel blocker glibenclamide 1 micro M, or the beta-adrenergic antagonist propranolol 1 micro M. Both T3 and T4 demonstrated concentration-dependent dilation of the U46619-preconstricted vessels (P < 0.001 each), with T3 having a greater effect than T4 (P < 0.05) (36% +/- 9% [mean +/- SD] dilation at 10-7 M T3 vs 24% +/- 6% dilation at 10-7 M T4). In comparison, isoproterenol 10-7 M produced 56% +/- 6% dilation. T3-mediated vasodilation was attenuated but not abolished by endothelial denudation (18% +/- 3% dilation at 10-7 M T3) (P < 0.01), L-NNA (15% +/- 7% dilation at 10-7 M T3) (P < 0.01), indomethacin (20% +/- 9% dilation at 10-7 M T3) (P < 0.05), and glibenclamide (22% +/- 7% dilation at 10-7 M T3) (P < 0.01), but it was not affected by propranolol (37% +/- 20% dilation at 10-7 M T3) (P = 0.99). We conclude that thyroid hormones possess direct vasodilatory effects with both endothelium-independent and endothelium-dependent components. Implications: Thyroid hormones may have modest direct vasodilatory effects. This may partially account for the cardiovascular actions of the hormones in hyperthyroidism or when administered pharmacologically in cardiac surgery. (Anesth Analg 1997;85:734-8)

Microvascular endothelial dysfunction and its mechanism in a rat model of subarachnoid hemorrhage

After subarachnoid hemorrhage (SAH), large cerebral arteries are prone to vasospasm. Using a rat model of SAH, we examined whether cortical microvessels demonstrate vasomotor changes that may make them prone to spasm and whether endothelial dysfunction may account for any observed changes. Two days after percutaneous catheterization into the cisterna magna, 0.3 mL of autologous blood was injected into the subarachnoid space. The brain tissue was harvested 20 min later, and microvessels were dissected from the parietal cortex. Vasomotor responses to the thromboxane analog U46619, the protein kinase C agonist phorbol acetate, endothelin-1, adenosine diphosphate, nitroprusside, and isoproterenol were examined in vitro in cerebral arterioles from the control, sham-operated, and SAH animals. Endothelial nitric oxide synthase (NOS3) messenger RNA and protein concentration was measured by northern and western blotting, respectively. Arterioles from the SAH animals demonstrated attenuated dilation to the endothelium-dependent dilator adenosine diphosphate and accentuated constriction to endothelin-1, while responses to the other agents tested were unchanged. NOS3 protein concentration was decreased, but NOS3 messenger RNA was increased after SAH. After SAH, cortical arterioles demonstrate endothelial dysfunction, which may be the basis for microvascular spasm. This is in part related to decreased NOS3, which occurs despite an increase in its transcription.

Propofol-associated dilation of rat distal coronary arteries is mediated by multiple substances, including endothelium-derived nitric oxide

Previous in vitro studies on the effect of propofol on coronary arteries have shown variable results, ranging from constriction to no effect to dilation.Although most of these studies reported that the observed effect is endothelium-independent, propofol also releases nitric oxide from cultured porcine endothelial cells. The present study examines the direct effect of propofol in rat distal coronary arteries in vitro, especially in regard to endothelial dependence and involvement of the adenosine triphosphate (ATP)-sensitive potassium channels (KATP channels). Forty-three subepicardial arteries (size 91.1 +/- 15.8 micro meter) from Wistar rats were studied in vitro in a no-flow, pressurized (40 mm Hg) state, using an optical density video detection system. After preconstriction with the thromboxane analog U46619 1 micro Meter, relaxation responses to increasing concentrations of propofol (10-6-10 (-4) M) were measured after 1) endothelial denudation, 2) pretreatment with the nitric oxide synthase inhibitor NG-nitro-L-arginine (L-NNA), 3) pretreatment with the cyclooxygenase inhibitor indomethacin, 4) pretreatment with the KATP channel blocker glibenclamide, or 5) no intervention (control). Propofol produced a significant concentration-dependent vasodilation of the U46619-preconstricted coronary arteries. This effect was significantly attenuated by endothelial denudation, pretreatment with L-NNA, or indomethacin, but was not affected by glibenclamide. We conclude that propofol has a direct vasodilatory effect on distal coronary arteries in rats. This effect is primarily endothelium-dependent and is mediated by multiple substances, including nitric oxide (NO) and a vasodilatory prostanoid. The effect is not mediated by opening of the KATP channels. (Anesth Analg 1995;81:1191-6)

Perioperative and long-term morbidity and mortality after above-knee and below-knee amputations in diabetics and nondiabetics.

We performed a retrospective review of a vascular surgery quality assurance database to evaluate the perioperative and long-term morbidity and mortality of above-knee amputations (AKA, n = 234) and below-knee amputations (BKA, n = 720) and to examine the effect of diabetes mellitus (DM) (181 of AKA and 606 of BKA patients). All patients in the database who had AKA or BKA from 1990 to May 2001 were included in the study. Perioperative 30-day cardiac morbidity and mortality and 3-yr and 10-yr mortality after AKA or BKA were assessed. The effect of DM on 30-day cardiac outcome was assessed by multivariate logistic regression and the effect on long-term survival was assessed by Cox regression analysis. The perioperative cardiac event rate (cardiac death or nonfatal myocardial infarction) was at least 6.8% after AKA and at most 3.6% after BKA. Median survival was significantly less after AKA (20 mo) than BKA (52 mo) (P < 0.001). DM was not a significant predictor of perioperative 30-day mortality (odds ratio, 0.76 [0.39–1.49]; P = 0.43) or 3-yr survival (Hazard ratio, 1.03 [0.86–1.24]; P = 0.72) but predicted 10-yr mortality (Hazard ratio, 1.34 [1.04–1.73]; P = 0.026). Significant predictors of the 30-day perioperative mortality were the site of amputation (odds ratio, 4.35 [2.56–7.14]; P < 0.001) and history of renal insufficiency (odds ratio, 2.15 [1.13–4.08]; P = 0.019). AKA should be triaged as a high-risk surgery while BKA is an intermediate-risk surgery. Long-term survival after AKA or BKA is poor, regardless of the presence of DM.

Protamine and protamine reactions.

First discovered in 1868, protamine is a polycationic, alkaline protein molecule, made up of two-thirds arginine residues and one-third other amino acids. Heads of the sperm of the salmonidae or clupeidae family as well as man are rich in protamine, and salmon milt is the commercial source of protamine. Clinical uses of protamine include the neutralization of heparin used during cardiac or vascular surgery, cardiac catheterization, dialysis and phoresis, and the retardation of insulin absorption in intermediateand long-acting insulin preparations. Because protamine is positively charged, it forms a stable complex with the negatively charged heparin, a heterogeneous compound with alternating residues of iduronic acid and glucosamine; iduronic acid contains 2 sulfate groups and is one of the strongest naturally occurring acids. The protamine–heparin complex is devoid of anticoagulant activities. Protamine-containing insulin preparations are neutral protamine Hagedorn (NPH) insulin and protamine zinc insulin (PZI). Each unit of NPH insulin contains 3 to 6 μg of protamine, and each unit of PZI has 10 to 15 μg of protamine.

Heterogeneous Vasomotor Responses of Rabbit Coronary Microvessels to Isoflurane

BackgroundPrevious in vitro studies on the mechanism of isoflurane-elicited vasodilation have examined conductance arteries and reported conflicting data on whether the vasomotor response Is mediated through the release of endothelium-derived nitric oxide. The current study was undertaken to define the effect of isoflurane on both resistance and conductance coronary arteries in rabbits and to elucidate the mechanism of the effect. MethodsRabbit coronary arteries of varying sizes were dissected and each placed in a microvessel chamber. The arteries were studied in a pressurized (40 mmHg), no-flow state and were exposed to increasing concentrations of isoflurane, 0–3%, by an in-line bubble-through vaporizer. The vessel lumen diameter was monitored using an optical density video detection system. Selected experiments were performed on micro-vessels after preincubation with indomethacin, NG-monomethyl-L-arginine, or methylene blue or after endothelial denudation. ResultsIsoflurane caused a dose-dependent constriction of small rabbit coronary arteries (internal diameter of 139 ± 34 μ, mean ± SD), whereas it caused dilation of large coronary arteries (371 ± 54 μ). The vasoconstriction of the small coronary arteries by isoflurane was abolished by endothelial denudation or after preincubation with indomethacin. The vasodilation of the large vessels by isoflurane was inhibited by endothelial denudation or after preincubation with NG-monomethyl-L-arglnine, methylene blue, or indomethacin. ConclusionsOur data suggest that vessel size is a determinant of the vasomotor response to isoflurane. Exposure to isoflurane produces vasodilation of conductance coronary arteries, whereas it is associated with vasoconstriction of resistance coronary microvessels. The latter appears to be endothelium-dependent and mediated by cyclooxygenase produces), whereas the former, also endothelium-dependent, is mediated by both product(s) of cyclooxygenase and endothelium-derived nitric oxide.

General anesthesia versus regional anesthesia.

No distinct advantage is apparent between regional and general anesthesia when considering perioperative cardiac morbidity and mortality in peripheral vascular surgery. However, there is some evidence to support regional anesthesia over general anesthesia in an effort to optimize graft patency if the regional technique is extended into the postoperative period to provide neuraxial analgesia. An inadequate number of randomized, controlled trials have been conducted to determine whether regional or general anesthesia should be performed for carotid endarterectomy. The nonrandomized trials do support regional anesthesia by virtue of reductions in stroke, myocardial infarction, and death. A randomized, prospective trial is needed to verify these outcomes. The choice of technique does not appear to affect mortality in patients requiring hip fracture surgery, although Urwin et al. (29) reported less 1-month mortality in patients receiving regional anesthesia. General anesthesia has been associated with increased blood loss and thromboembolic complications in patients undergoing hip fracture repair. Epidural anesthesia has been shown to promote quicker return of bowel function postoperatively when the catheter has been sited at T12 or higher. Anastomotic breakdown in patients with epidural anesthesia/analgesia has rarely been reported. Most studies tend to show quicker return of bowel function when local anesthetics alone are administered epidurally.

Preoperative Cardiology Consultation

In a 1998 survey of New York metropolitan area anesthesiologists, surgeons, and cardiologists, the three specialties were in general agreement that important purposes of a cardiology consultation are to treat an inadequately treated cardiac condition before surgery (e.g., unstable angina or congestive heart failure [CHF]), to provide data to use in anesthesia management (e.g., ischemic threshold of tachycardia on stress test or left ventricular ejection fraction), and possibly to diagnose a medical condition before surgery (e.g., the cause of a new-onset atrial fibrillation). The yield of a cardiology consultation, in terms of new therapy or significant effect on patient management strategy prior to surgery, has, however, been reported to vary widely from 10% to more than 70%. The reasons why the consultation process often falls short of ideal are probably multifold, but may often originate from vague understanding of the consultation process. The physician initiating the consultation, whether an anesthesiologist or a surgeon, may not make it clear to the cardiologist why the consultation is being sought. In a retrospective review of 202 cardiology consultations at a university hospital, it was found that 108 just asked for an “evaluation,” 79 asked for a “clearance,” and 9 did not specifically request anything. Only six posed a specific question. As a result, the consultant often makes broadly inclusive, general remarks about perioperative management of the patient and may recommend preoperative diagnostic work-up that does not influence the patient’s outcome but prolongs the hospital stay. In this review are presented (1) the indications for cardiology consultations as implied in the American College of Cardiology–American Heart Association (ACC–AHA) guidelines on preoperative cardiac evaluation, and (2) suggestions on how the ACC–AHA guidelines may be critically applied to, and improve, the consultation process. Preoperative Cardiac Consultation Based on the ACC–AHA Guidelines The ACC–AHA guidelines on preoperative cardiac evaluation were published initially in 1996 and were also endorsed by the Society of Cardiovascular Anesthesiologists and the Society for Vascular Surgery. An updated version of the guidelines was published in 2002. The guidelines were based on the then-available literature as well as expert opinions from the disciplines of anesthesiology, cardiology, electrophysiology, vascular medicine, vascular surgery, and noninvasive cardiac testing. The guidelines provided an 8-step algorithm for stratifying the patient’s risks and triaging to either surgery or cardiac evaluation. The first three steps of the guidelines consider the urgency of the operation and the recency of cardiac evaluation and intervention. If the operation is not emergent and if there has not been recent cardiac evaluation and/or intervention with no significant interim changes, then the remainder of the guidelines are applied. Steps 4 through 7 deal with an assessment of the patient’s clinical predictors of cardiac risk, functional status, and the risk of the surgery proposed. Step 8, or noninvasive cardiac testing to further define the patient’s risk, is indicated (1) if the patient has a major clinical predictor, (2) if the patient has an intermediate clinical predictor and either has poor functional status or is undergoing a high-risk surgery, or (3) if the patient has poor functional status and is undergoing a high-risk surgery. As defined by the ACC–AHA, major clinical predictors are unstable coronary syndrome, decompensated congestive heart failure (CHF), significant arrhythmias, and severe valvular disease. Intermediate clinical predictors are mild angina pectoris, history of myocardial infarction (MI) or CHF, diabetes mellitus, and chronic renal failure with serum creatinine greater than 2 mg/dl. A high-risk surgery carries a greater than 5% perioperative risk of cardiac events such as MI, CHF, or death and is exemplified by emergent major operations, especially in the elderly, aortic, and other major vascular procedures, peripheral vascular bypass procedures, and anticipated prolonged surgical procedures associated with large fluid shifts and/or blood loss. An intermediate-risk surgery carries 1–5% perioperative risk of cardiac events and is exemplified by carotid endarterectomy, intraperitoneal and Director of Vascular Anesthesia, Department of Anesthesia & Critical Care, Beth Israel Deaconess Medical Center, and Associate Professor of Anaesthesia, Harvard Medical School.

Epithelial Dependence of the Bronchodilatory Effect of Sevoflurane and Desflurane in Rat Distal Bronchi

The bronchial epithelium releases substances that enhance bronchodilation in response to certain bronchodilators.We examined the hypothesis that the bronchodilatory effect of desflurane and sevoflurane depends on the epithelium in rat distal bronchial segments. Wistar rat subsegmental bronchial segments (diameter approximately 100 [micro sign]m) were dissected. After preconstriction with 5-hydroxytryptamine, each segment was exposed to increasing concentrations of desflurane 0%-12% or sevoflurane 0%-4.8% under four conditions: after epithelial rubbing, after pretreatment with the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA), after pretreatment with the cyclooxygenase inhibitor indomethacin, or with no preintervention (control). Changes in bronchial diameter were monitored using an in vitro video detection system. Both desflurane and sevoflurane produced concentration-dependent bronchodilation (P < 0.001 for either anesthetic; 54% +/- 8% [mean +/- SD] dilation for 12% desflurane and 48% +/- 14% dilation for 4.8% sevoflurane). For both anesthetics, bronchodilation was significantly attenuated by epithelial rubbing (15% +/- 4% dilation for 12% desflurane and 13% +/- 10% dilation for 4.8% sevoflurane; P < 0.001 each), by pretreatment with indomethacin (12% +/- 3% dilation for 12% desflurane and 9% +/- 5% dilation for 4.8% sevoflurane; P < 0.001 each), and by L-NNA (24% +/- 8% dilation for 12% desflurane, P < 0.001; and 17% +/- 10% dilation for 4.8% sevoflurane, P < 0.01). Desflurane- and sevoflurane-mediated bronchodilation depends at least partially on the epithelium, and may involve both a prostanoid and NO in rat distal bronchi. Implications: Bronchodilation by the volatile anesthetics desflurane and sevoflurane is at least partially epithelium-dependent and may be attenuated in diseases affecting the epithelium, such as asthma. (Anesth Analg 1998;86:646-51)

Timing of high-risk vascular surgery following coronary artery bypass surgery: a 10-year experience from an academic medical centre.

Major non‐cardiac surgery within 40 days of coronary angioplasty with stenting has high cardiac complication rates. We have performed a case‐control study to determine whether the risk of vascular surgery might have increased in recent survivors of coronary artery bypass surgery (CABG). Using our vascular database from 1990 to 1999, we matched the cases who had vascular surgery within a month of CABG with controls by pre‐operative comorbidities of diabetes mellitus, history of myocardial infarction (MI), history of congestive heart failure (CHF), and chronic renal insufficiency and compared the incidence of peri‐operative MI, CHF, death, and other complications. Compared to case‐matched controls, patients who underwent vascular surgery within a month of CABG suffered significantly greater mortality (20.6% vs. 3.9%, p < 0.005). The incidence of non‐fatal cardiac complications was not significantly different between the groups. We conclude that the risk of mortality may be significantly greater in patients undergoing major vascular surgery within a month of CABG.