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Biomedical subjects

G W He

Publications and source records attributed to G W He.

At least 37 records · Page 2Linked to original sources

Effects of potassium channel opener KRN4884 on human conduit arteries used as coronary bypass grafts.

AIMS: The effects of a new potassium channel opener KRN4884 on human arteries have not been studied. This study was designed to investigate the effects of KRN4884 on the human internal mammary artery (IMA) in order to provide information on possible clinical applications of KRN4884 for preventing and relieving vasospasm of arterial grafts in coronary artery bypass grafting. METHODS: IMA segments (n = 140) taken from patients undergoing coronary surgery were studied in the organ chamber. Concentration-relaxation curves for KRN4884 were established in the IMA precontracted with noradrenaline (NA), 5-hydroxytryptamine (5-HT), angiotensin II (ANG II), and endothelin-1 (ET-1). The effect of glibenclamide (GBC) on the KRN4884-induced relaxation was also examined in NA or 5-HT-precontracted IMA. Concentration-contraction curves for the four vasoconstrictors were constructed without/with pretreatment of KNR4884 (1 or 30 microM) for 15 min. RESULTS: KRN4884 induced less relaxation (P < 0.05) in the precontraction induced by ET-1 (72.9 +/- 5.5%) than by ANG II (94.2 +/- 3.2%) or NA (93.7 +/- 4.1%) with lower EC50 (P < 0.05) for ANG II (-8.54 +/- 0.54 log M) than that for NA (-6.14 +/- 0.15 log M) or ET-1 (-6.69 +/- 0.34 log M). The relaxation in the IMA pretreated with GBC was less than that in control (P < 0.05). KRN4884-pretreatment significantly reduced the contraction (P < 0.05) induced by NA (151.3 +/- 18.4% vs 82.7 +/- 8. 7%), 5-HT (82.7 +/- 12.2% vs 30.1 +/- 7.3%), and ANG II (24.3 +/- 6. 3% vs 5.4 +/- 1.6%), but did not significantly reduce the contraction induced by ET-1 (P > 0.05). CONCLUSION: KRN4884 has marked vasorelaxant effects on the human IMA contracted by a variety of vasoconstrictors and the effect is vasoconstrictor-selective.

Aged↗

Arterial grafts for coronary artery bypass grafting: biological characteristics, functional classification, and clinical choice.

Various arterial grafts have been used for coronary artery bypass grafting, but a unanimous opinion on how to best use these grafts has not been formed. Arterial grafts are not uniform in their biological characteristics. Differences between the perioperative behavior of the grafts and their long-term patency may be related to different characteristics. These characteristics should be taken into account in the use of arterial grafts, some of which are subject to more active pharmacologic intervention during and after operation to obtain satisfactory results. Clinical choice of grafts must be based on the general condition of the patient, the biological characteristics of the graft, the anatomy of the coronary artery, the match between the coronary artery and the graft, and technical considerations, including antispastic management.

Arteries↗

Pharmacology of coronary artery bypass grafts.

Spasm of arterial and venous graft conduits can occur both during harvesting and after the graft is connected. Attempts to overcome spasm during harvesting by probing or hydraulic distension can cause structural damage to the graft, which may impair short- and long-term patency. After a coronary artery bypass graft is connected, spasm can cause major problems with myocardial perfusion. To select the best pharmacologic agent to prevent or reverse vasoconstriction in a graft requires an understanding of the reactivity of that particular type of graft to vasoconstrictor and vasodilator agents. The pharmacologic reactivity of venous and arterial graft conduits has been documented through extensive studies of isolated vessels in the organ bath and of in situ grafts in the body. In this review we summarize the current state of knowledge of the reactivity of arterial and venous grafts to vasoconstrictor and vasodilator agents and describe the practical application of this knowledge in the operating room and in the postoperative period.

Arteries↗

Altered endothelium-derived hyperpolarizing factor-mediated endothelial function in coronary microarteries by St Thomas' Hospital solution.

OBJECTIVES: We examined the effect of St Thomas' Hospital solution on endothelium-derived hyperpolarizing factor-mediated function in the porcine coronary microarteries with emphasis on the effect of temperature and washout time. METHODS: Microartery rings (diameter, 200-450 micrometers) were studied in myograph. The arteries were incubated in St Thomas' Hospital or Krebs solution (control) at 4 degrees C for 4 hours followed by 45 minutes (group Ia) or 90 minutes washout (group Ib) or at 22 degrees C for 1 hour followed by 45 minutes (group IIa) or 90 minutes washout (group IIb) and precontracted with -8.5 log M U 46619. The endothelium-derived hyperpolarizing factor-mediated relaxation to bradykinin was studied when endothelium-derived nitric oxide and prostaglandin I2 were inhibited with the presence of 7 micromol/L indomethacin and 300 micromol/L NG-nitro-L -arginine. RESULTS: After exposure to St Thomas' Hospital solution, the maximal endothelium-derived hyperpolarizing factor-mediated relaxation (percentage of the precontraction) was significantly reduced at either temperature after washout for 45 minutes (group Ia, 42.7% +/- 3.5% vs 69.0% +/- 5.3%; n = 9; P =.000; and group IIa, 12.3% +/- 1.6% vs 56.1% +/- 4. 4%; n = 8; P =.000) but fully recovered after washout for 90 minutes. The U46619-induced contraction force was also significantly reduced after washout for 45 minutes (P <.001) but fully recovered at 90 minutes. CONCLUSIONS: Under profound and moderate hypothermia, St Thomas' Hospital solution impairs endothelium-derived hyperpolarizing factor-mediated relaxation and smooth muscle contraction in the coronary microarteries. These effects exist during the reperfusion period for at least 45 minutes after exposure to St Thomas' Hospital solution and may account for the possible myocardial dysfunction during reperfusion.

Animals↗

Comparison of the vasorelaxant effect of nitroprusside and nitroglycerin in the human radial artery in vitro.

AIMS: In recent years the radial artery (RA) has been re-introduced for coronary artery bypass grafting (CABG). However, the potential for vasospasm remains a clinical problem when this vessel is employed and effective vasodilator agents are required to combat vasospastic events. This in vitro study was designed to compare the vasodilator effects of sodium nitroprusside (SNP) and nitroglycerin (NTG) in the human RA. METHODS: Human RA segments (n=70) were taken from vessels employed for grafting in patients undergoing CABG. Concentration-relaxation curves for SNP and NTG were established in RA which had been precontracted with various vasoconstrictors (potassium chloride [K+], the thromboxane A2 mimetic agent U46619 or endothelin-1 [ET-1]). RESULTS: Both SNP and NTG caused complete relaxation and EC50s were similar except that NTG was 6.2-fold more potent than SNP in U46619-induced contraction (-7.50+/-0.16 vs -6. 71+/-0.38 log m, P=0.04). After treatment with verapamil and NTG solution during harvesting, the RA segments responded with reduced maximal relaxation to NTG (84.9+/-3.9%, compared with 98.8+/-0.8% in the control, P=0.004). The vessel became less sensitive to NTG (EC50: -6.29+/-0.4 vs -7.50+/-0.16 log m, P=0.01). In investigations carried out with SNP, tolerance was only seen in the magnitude of the relaxation (87.4+/-4.7% vs 99.2+/-0.6% in the control, P=0.03). CONCLUSIONS: Both NTG and SNP are potent vasodilators in the RA. NTG may have more potent effects in certain situations (constriction related to thromboxane A2). However, tolerance to NTG may develop. A cross tolerance to SNP may exist but the effect is weak so that SNP may be preferable to NTG as a vasodilator in the RA postoperatively. Other vasodilators may be the drugs of choice under such circumstances.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Inhibition of vasoconstriction by the thromboxane A2 antagonist GR32191B in the human radial artery.

AIMS: The newly revived coronary bypass graft, the radial artery (RA), is more spastic than the internal mammary artery. Thromboxane A2 is a potent vasoconstrictor for arterial grafts. This study was therefore designed to determine whether the specific thromboxane A2 (TP) receptor antagonist, GR32191B, is effective in inhibition of prostanoid or nonprostanoid receptors in the RA. METHODS: The effect of GR32191B was studied in human RA segments, taken from coronary bypass patients, in organ chambers. Two effects of GR32191B were tested: (1) the relaxation induced by GR32191B in the RA precontracted with the TP receptor agonists U46619 and PGF2alpha or nonprostanoid vasoconstrictors (noradrenaline [NA], angiotensin II [AII], and K+ ) and (2) the inhibitory effect of GR32191B on TP receptor agonists and nonprostanoid vasoconstrictors. RESULTS: In U46619 (10 nm, n=7) and PGF2alpha (1 microm, n=7) precontracted RA, GR32191B induced 100% relaxation (10-100 microm ) but not after precontraction with nonprostanoid stimuli (5.8% for K+, 25 mm, n=6, 24.4% for NA, 3 microm, n=8, and 53.2% for AII, 3 nm, n=5) (P<0.001). Treatment with GR32191B (30 nm ) significantly depressed the contraction with U46619 (from 160.1+/-11.0% to 116.8+/-13.1%, P<0. 05) or PGF2alpha (from 91.3+/-12.3% to 42.2+/-9.2%, P<0.01). The contraction was further abolished by 3 microm GR32191B. However, GR32191B at 3 microm did not significantly inhibit the contraction induced by either NA, AII, or K+. CONCLUSIONS: GR32191B is a highly potent and specific TP receptor antagonist for the human RA. It may be particularly useful in inhibiting TXA2-mediated vasoconstriction and therefore in reducing the complications related to vasospasm in this graft.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Myocardial protection during cardiac surgery from the viewpoint of coronary endothelial function.

1. During cardiac surgery, the heart is arrested and subject to ischaemia-reperfusion injury. 2. To protect the heart, cardioplegia is usually used to initially stop and then maintain the still condition of the heart, which not only facilitates the precise operation but, more importantly, minimizes the energy consumption of the heart during this period. 3. The ischaemia-reperfusion injury may involve both myocytes and coronary endothelium-smooth muscle and, therefore, the protection of the heart should also involve these two aspects. 4. Injury to the heart involves: (i) ischaemia-reperfusion injury to the myocytes and coronary circulation; and (ii) possible injury to the coronary circulation by cardioplegia due to its hyperkalaemic components. 5. Injury to the coronary circulation may involve both endothelium-derived nitric oxide (EDNO) and endothelium-derived hyperpolarizing factor (EDHF) mechanisms. The EDNO mechanism is susceptible to ischaemia-reperfusion, whereas the EDHF mechanism may be altered by hyperkalaemic cardioplegia. 6. To further protect the heart, supplemental therapy for EDNO and optimizing the components of cardioplegia to restore the EDHF mechanism may be important.

Animals↗

Surgical management of blunt traumatic rupture of the descending thoracic aorta.

Acute rupture of the descending thoracic aorta following blunt trauma is a life-threatening injury that requires emergent operative intervention. From February 1989 to January 1997, 4 patients with multiple injuries including traumatic rupture in the region of the aortic isthmus were surgically treated at our institution. Diagnosis was confirmed in all patients by aortogram prior to aortic repair. One patient had preoperative paraplegia secondary to an unstable spinal fracture. All patients underwent repair under cardiopulmonary bypass (3 partial, 1 total with hypothermic arrest). The site of rupture was resected and replaced with an interposition artificial graft. There was no perioperative mortality and no additional occurrence of paraplegia. Our experience and a review of the literature indicate that for survivors of traumatic aortic rupture, excellent outcomes can be achieved only if the diagnosis is made early and the surgical treatment is prompt.

Acute Disease↗

Repair of ruptured sinus of valsalva aneurysm: determinants of long-term survival.

BACKGROUND: Ruptured sinus of Valsalva aneurysm is a rare cardiac anomaly and long-term survival after surgical treatment is not well established. This study was designed to investigate the determinants of long-term survival after repair of ruptured sinus of Valsalva aneurysm. METHODS: From April 1978 to April 1996, 53 patients underwent operation for ruptured sinus of Valsalva aneurysm. The incidence among our cardiac surgical population was 0.56%. Long-term survival was investigated in 46 patients (13 to 65 years) who survived the operation, with 96.2% follow-up completeness (mean+/-standard deviation, 6.5+/-4.9 years; maximum, 17.2 years), by univariate and multivariate analyses. RESULTS: There was no early operative death and no recurrence after the initial repair. Actuarial survival was 83.8%+/-8.4% at 15 years. Reoperation, aneurysm draining into the left ventricle, aortic prosthetic dehiscence, bacterial endocarditis, and aortic cross-clamp time (<70 minutes) were significant factors in long-term survival (p < 0.05). Multivariate analysis revealed that only aortic prosthesis dehiscence was the significant factor influencing late survival (p = 0.0001). CONCLUSIONS: Surgical treatment for ruptured sinus of Valsalva aneurysm is safe and has satisfactory results. Aortic prosthesis dehiscence is the independent determinant for long-term survival. Other factors including bacterial endocarditis, concomitant ventricular septal defect repair, and aortic valve replacement did not independently influence long-term survival.

Adolescent↗

Potassium-channel opener in cardioplegia may restore coronary endothelial function.

BACKGROUND: Depolarizing (hyperkalemic) solutions impair the coronary endothelial function through an endothelium-derived hyperpolarizing factor mechanism. I examined the hypothesis that potassium-channel openers may restore the impaired endothelium-derived hyperpolarizing factor-mediated coronary vasorelaxation when added to hyperkalemic cardioplegia. METHODS: The porcine coronary arteries were exposed to hyperkalemia (potassium, 20 or 50 mmol/L) or hyperkalemia plus the potassium-channel opener aprikalim at 0.1 mmol/L for 1 hour. Endothelium-derived hyperpolarizing factor-mediated relaxation (percentage of 30 nmol/L U46619 precontraction) was induced by calcium ionophore A23187 and bradykinin in the presence of indomethacin (7 micromol/L) and Nomega-nitro-L-arginine (300 micromol/L). RESULTS: The endothelium-derived hyperpolarizing factor-mediated relaxation was significantly impaired by exposure to hyperkalemia (20 mmol/L: 24.9%+/-14.1% versus 88.0%+/-3.3% in control, p = 0.002 for A23187; 50 mmol/L: 40.5%+/-12.3% versus 76.5%+/-3.8%, p = 0.003 for bradykinin). This reduced relaxation was significantly recovered by addition of aprikalim into the hyperkalemic (20 mmol/L) solution in A23187 experiments (81.2%+/-4.8%, p = 0.002) but only slightly recovered when added into the higher concentration of potassium (50 mmol/L) in bradykinin experiments (56.1%+/-4.7%, p = 0.2). CONCLUSIONS: Potassium-channel openers may preserve endothelium-derived hyperpolarizing factor-mediated coronary relaxation when added to traditional hyperkalemic cardioplegia. This effect is significant when the potassium concentration is 20 mmol/L but partially lost when it reaches 50 mmol/L. This study may provide new insights into cardioprotection during open heart operations.

Animals↗

Verapamil plus nitroglycerin solution maximally preserves endothelial function of the radial artery: comparison with papaverine solution.

BACKGROUND: Endothelium plays a key role in graft patency. My colleagues and I have developed a verapamil+nitroglycerin solution (balanced to pH 7.4) to prepare the radial artery without mechanical distention or dilation and have reported the efficacy of its antispastic action. This study was designed to investigate whether using this solution as part of the University of Hong Kong protocol to prepare the radial artery is more efficacious than papaverine solution in preserving endothelial function. METHODS: Ring segments of the radial artery taken from 25 patients undergoing coronary artery bypass grafting were studied in organ chambers. The endothelium-dependent relaxation, as the index of endothelial function, was examined by two mechanisms-receptor-mediated relaxation (by acetylcholine) and non-receptor-mediated relaxation (by calcium ionophore A23187) in U46619-induced contraction (10 nmol/L). RESULTS: In the relaxation induced by either acetylcholine (27.3% +/- 5.0% [n = 7] vs 23.9% +/- 3.9% [n = 6],p = 0.6) or A23187 (62.9% +/- 6.0% [n = 13] vs 62.3% +/- 8.4% [n = 6],p = 0.96), there was no significant difference between the control radial arteries and those treated with the verapamil+nitroglycerin solution. In the papaverine-treated rings, acetylcholine-mediated relaxation was abolished (3.3% +/- 2.6% vs 23.9% +/- 3.9%,p < 0.001) and A23187-mediated relaxation was significantly reduced (39.7% +/- 5.2% vs 62.3% +/- 8.4%, p = 0.02) compared with verapamil+nitroglycerin treatment. CONCLUSION: Use of verapamil+nitroglycerin solution to prepare the radial artery maximally preserves endothelial function. In contrast, papaverine impairs this function. Verapamil+nitroglycerin solution may be effectively and safely used to prepare the radial artery for coronary artery bypass grafting.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Impaired endothelium-derived hyperpolarizing factor-mediated relaxation in coronary arteries by cold storage with University of Wisconsin solution.

OBJECTIVES: University of Wisconsin solution is widely used to preserve organs for transplantation, but its effect on the individual endothelium-derived relaxing factors has not been studied. This study was designed to examine the effect of cold storage of the heart with University of Wisconsin solution on relaxation mediated by the endothelium-derived hyperpolarizing factor (EDHF). METHODS: Porcine coronary artery rings were studied in organ chambers. Relaxation in response to the EDHFs stimuli bradykinin and A23187 in U46619 (30 nmol/L)-induced precontraction after incubation with University of Wisconsin solution (either at 37 degrees C in the oxygenated organ chamber or at 4 degrees C in a refrigerator for 4 hours) was compared with the control. RESULTS: During the incubation, the coronary tone initially increased transiently (4.8 +/- 0.8 gm) and was subsequently reduced by 10.9 +/- 1.2 gm. Under both normothermia and hypothermia, after the incubation, the relaxation mediated by EDHF significantly decreased (under normothermia: from 68.7% +/- 10.2% to 32.1% +/- 8%, n = 7, p = 0.001, for bradykinin and from 79.9% +/- 8.4% to 56.9% +/- 8.5%, n = 7, p = 0.01, for A23187; under hypothermia and hypoxia: to 18.9% +/- 5.6%, n = 9, p = 0.0005, for bradykinin and 52.7% +/- 7.5%, n = 9, p = 0.03, for A23187). The incubation at normothermia also impaired the coronary smooth muscle contractility to U46619, but this contractility was preserved by cold storage. CONCLUSIONS: During cold storage, University of Wisconsin solution impairs the endothelium-dependent relaxation mediated by EDHF in the coronary circulation. This effect exists after the storage for at least 1 hour.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Characteristics of adrenoceptors in the human radial artery: clinical implications.

OBJECTIVES: The radial artery has been suggested to be spastic. Endogenous and exogenous catecholamines and the use of beta-blockers may be related to radial artery spasm, but the characteristics of adrenoceptors in this artery are unknown. This study was designed to characterize the alpha- and beta-adrenoceptor in the human radial artery. METHODS: Ring segments of the radial artery (n = 59) taken from patients undergoing coronary artery bypass grafting were studied in organ chambers. Alpha-adrenoceptor agonists (norepinephrine, methoxamine, and UK14304) and antagonists (phentolamine hydrochloride [INN: phentolamine], prazosin, and yohimbine) were used to characterize the alpha-adrenoceptor. Beta-adrenoceptor function was studied in U46619-precontracted rings in response to isoproterenol (INN: isoprenaline). RESULTS: Norepinephrine induced 6.9 +/- 0.6 gm (80.6% +/- 6.8% of the contraction by 100 mmol/L KCl), and this was almost fully inhibited by phentolamine hydrochloride (10 micromol/L, p < 0.0001). The contraction force induced by methoxamine (2.9 +/- 0.8 gm) was abolished by 0.5 micromol/L prazosin (p = 0.017). The contraction force induced by UK14304 (1.7 +/- 0.4 gm) was abolished by 1 micromol/L yohimbine. In contrast to the porcine coronary artery used as the control (fully relaxed to isoproterenol), radial artery rings did not have significant relaxation (1.1% +/- 0.8%). CONCLUSIONS: The human radial artery is an alpha-adrenoceptor-dominant artery with little beta-adrenoceptor function. The use of beta-blockers will not likely evoke the spasm of the radial artery. Furthermore, the radial artery has a dominant alpha1-adrenoceptor function, but the postjunctional alpha2-adrenoceptor is also functional. Circulating catecholamines will mainly contract the human radial artery by activation of the alpha1-adrenoceptors and to a lesser extent also by alpha2-adrenoceptors.

Adrenergic Agonists↗

Effect and mechanism of cardioplegic arrest on the coronary endothelium-smooth muscle interaction.

1. During cardiac surgery, the heart is arrested and protected by hyperkalaemic cardioplegia. The coronary endothelium may be damaged by ischaemia-reperfusion and cardioplegia. Subsequently, this may affect cardiac function immediately after cardiac surgery and cause mortality and morbidity. 2. We investigated coronary endothelium-smooth muscle interaction after exposure to depolarizing (hyperkalaemic; K+ 20 or 50 mmol/L) and hyperpolarizing (the K+ channel opener aprikalim) cardioplegia and organ preservation solution (University of Wisconsin (UW) solution). Endothelium-dependent relaxation and hyperpolarization of the coronary smooth muscle were studied in the porcine and human large conductance and micro-coronary arteries. Intracellular free calcium concentration in endothelial cells was also measured. 3. The endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation to A23187, bradykinin, and substance P in arteries contracted by either U46619 (10 nmol/L) or K+ (25 mmol/L) was reduced after exposure to either high K+ or UW solution, but was maximally preserved after exposure to aprikalim. The hyperpolarization of the membrane potential in response to the above endothelium-derived relaxing factor stimuli was also reduced by exposure to depolarizing cardioplegia. Studies in microcoronary arteries are in accordance with findings in large arteries. The intracellular free calcium concentration remained unchanged after exposure to hyperkalaemia. 4. We concluded that: (i) during cardiac surgery, the function of coronary circulation may be changed due to exposure to depolarizing cardioplegia or preservation solutions; (ii) the functional change in the coronary circulation is related to the altered interaction between the endothelium and smooth muscle; (iii) depolarizing (hyperkalaemia) cardioplegia or hyperkalaemic organ preservation solutions affect endothelium-smooth muscle interaction through the EDHF pathway; (iv) EDHF relaxes the porcine large and microcoronary arteries through multiple K+ channels; and (v) that hyperpolarizing vasodilators (K+ channel openers) may protect EDHF-mediated endothelial function when used as cardioplegia.

Animals↗

Risk factors for development of acute renal failure (ARF) requiring dialysis in patients undergoing cardiac surgery.

Acute renal failure (ARF) is one of the major complications after cardiopulmonary bypass for open heart operations. The present study was undertaken to identify the risk factors for the development of ARF following cardiopulmonary bypass (CPB). Four hundred and forty-seven consecutive patients who underwent open heart procedures from July 1994 to June 1995 were analyzed retrospectively. Their mean age was 55.6 +/- 14.2 (SD) years (range, 18 to 80). Dialysis was instituted whenever a patient exhibited inadequate urine output (<0.5 mL/kg/hr) for 2 to 3 hours despite correction of hemodynamic status and diuretic therapy, especially if fluid overload, hyperkalemia, or metabolic acidosis were also present. Twenty variables were analyzed by univariate analysis; these included nine preoperative variables--age, sex, hypertension, atherosclerosis, diabetes mellitus, left ventricular end-diastolic dimension (LVEDD) >5 cm, preoperative congestive heart failure, renal insufficiency (serum creatinine > or =130 micromol/L on two occasions), and sepsis--10 intraoperative variables--duration of CPB, redo procedures, emergency surgery, use of intraaortic balloon pump (IABP) in operating room, use of gentamicin, use of ceftriaxone, use of sulbactam/ampicillin, requirement of deep hypothermic circulatory arrest, duration of low mean perfusion pressure (mean pressure <50 mmHg for more than 30 minutes), operation on multiple valves--and one postoperative variable--significant hypotension (systolic blood pressure less than 90 mmHg for more than 1 hour). Significant variables or the variables having a trend (p<0.1) to be associated with ARF were included in stepwise multiple logistic regression analyses. Three regression analyses were performed separately. The incidence of ARF requiring dialysis in the study period was 15.0%. Significant risk factors for whole group of patients (regression I) were preoperative renal insufficiency (p<0.0001), postoperative hypotension (p<0.0001), cardiopulmonary bypass time more than 140 min (p<0.005), preoperative congestive heart failure (p<0.01), and history of diabetes mellitus (p<0.01). The risk factors in the valve group of patients (regression II) were preoperative renal insufficiency (p<0.0001) and postoperative hypotension (p<0.05). Risk factors in the CABG patients (regression III) were postoperative hypotension (p=0.0001), CPB time more than 140 min (p<0.05), preoperative renal insufficiency (p<0.05), and age (p<0.05). The authors conclude that preoperative renal insufficiency and postoperative hypotension are the most important independent risk factors for ARF in postcardiac surgical patients. In addition, CPB time greater than 140 minutes and old age are also independent risk factors for ARF in CABG patients. CPB time more than 140 minutes, history of diabetes mellitus, and preoperative congestive heart failure are independent risk factors for development of ARF in our total group of patients. These findings may have important clinical implications in the prevention of ARF in postcardiac surgical patients.

Acute Kidney Injury↗

A non-fatal impalement injury of the thorax.

Impalement is an uncommon injury with only occasional reports in the literature. There are even fewer reports of impalement injuries limited to the thorax. We report herein the case of a 24-year-old man who survived impalement injury of the left side of the thorax with a steel rod while working at a construction site. The great vessels of the thorax were spared but the second thoracic vertebra was fractured resulting in complete paralysis of the left lower limb. The precise nature and extent of the injury were determined pre-operatively by computed tomography and aortography. The important principles of surgical management contributing to the successful outcome are described, these being minimal manipulation of the impalement object before and during transport, careful pre-operative planning and a multidisciplinary approach.

Accidents, Occupational↗

Hyperkalemia exposure impairs EDHF-mediated endothelial function in the human coronary artery.

BACKGROUND: My colleagues and I have found in the porcine coronary artery that the pathway other than the nitric oxide (NG-nitro-L-arginine [L-NNA]-sensitive) and cyclooxygenase (indomethacin-sensitive) pathways of endothelium-dependent relaxation, related to the endothelium-derived hyperpolarizing factor (K+ channel-related), are altered after exposure to hyperkalemia. The present study was designed to examine whether this effect exists in the human coronary artery. METHODS: Coronary artery rings obtained from explanted fresh human hearts were studied in organ chambers under physiologic pressure. The endothelium-dependent relaxation in response to calcium ionophore A23187 was studied in U46619 (30 nmol/L)-induced precontraction in the presence of the cyclooxygenase inhibitor indomethacin (7 mumol/L) and the nitric oxide biosynthesis inhibitor L-NNA (300 mumol/L). The effect of incubation with 20 mmol/L K+ for 1 hour on the relaxation was examined in other coronary rings. RESULTS: In control rings, A23187 induced a maximal relaxation of 50.7% +/- 3.2% (n = 6). After 1 hour of exposure to 20 mmol/L K+, the relaxation was reduced to 30.4% +/- 4.6% (n = 6; p = 0.005). Incubation with hyperkalemia also significantly reduced the sensitivity (increased effective concentration that caused 50% of maximal relaxation) of the indomethacin- and L-NNA-resistant relaxation (-7.37 +/- 0.17 versus -8.28 +/- 0.27 log mol/L; p = 0.019). CONCLUSIONS: Exposure to hyperkalemia reduces the indomethacin- and L-NNA-resistant, endothelium-dependent (endothelium-derived hyperpolarizing factor-related) relaxation in the human coronary artery. This suggests that the previously proposed mechanism of coronary dysfunction after exposure to cardioplegic and organ preservation solutions in animal vessels is also valid in the human heart.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Surgical preparation abolishes endothelium-derived hyperpolarizing factor-mediated hyperpolarization in the human saphenous vein.

BACKGROUND: The impairment of the synthesis and release of endothelium-derived relaxing factors may be related to the high incidence of atherosclerosis and occlusion in saphenous vein grafts. This study focused on the effect of surgical preparation on one of the endothelium-derived relaxing factors, endothelium-derived hyperpolarizing factor, in the human saphenous vein. METHODS: Human saphenous vein segments taken from patients undergoing coronary bypass were placed in an organ bath. A glass microelectrode was inserted into a smooth muscle cell. The membrane potential in response to acetylcholine (-9 to -5 log M) was measured in normal or surgically prepared saphenous vein with presence or absence of NG-nitro-L-arginine (300 mumol/L) and indomethacin (7 mumol/L). RESULTS: The resting membrane potential was -71.28 +/- 1.91 mV (n = 7) with intact endothelium and -65.5 +/- 2.92 mV (n = 6, p > 0.05) without endothelium. Acetylcholine hyperpolarized membrane potential with intact endothelium (-90.57 +/- 1.48 mV, n = 7, p < 0.001), but not without endothelium (-69.67 +/- 2.93 mV, n = 6, p > 0.05). In the surgically prepared saphenous vein, acetylcholine did not hyperpolarize membrane potential (-71.83 +/- 3.84 mV versus the resting membrane potential of -69.50 +/- 3.53 mV, n = 6, p > 0.05). CONCLUSIONS: The endothelium-derived hyperpolarizing factor plays a role in the human saphenous vein. The surgical preparation abolishes the endothelium-derived hyperpolarizing factor-mediated hyperpolarization in the saphenous vein. This study provides evidence of functional changes of endothelium by traditional surgical preparation from another point of view, and it may be related to the high incidence of occlusion in saphenous vein grafts.

Biological Factors↗