[Cardiac surgery for patients with ventricular dysfunction].

Coronary artery disease and aortic stenosis/regurgitation may cause irreversible myocardial damage, resulting in significant heart failure. Although the ultimate treatment of the end-stage heart failure is heart transplantation or ventricular assist devices, in most cases these patients still have some amount of functional and survival benefit by simple surgical treatment such as coronary artery bypass grafting (CABG) and valve replacement. However it is associated with significant perioperative mortality and morbidity.

Effects of renal function on the pharmacokinetics and pharmacodynamics of prophylactic cefazolin in cardiothoracic surgery.

The purpose of this investigation was to study the effects of renal function on the pharmacokinetics and pharmacodynamics (PK-PD) of free cefazolin administered prophylactically in cardiothoracic surgery. Patients received an initial 2-g dose of cefazolin, followed by 1-g doses 6, 12, 18 and 24 h after the first dose. In patients who underwent cardiopulmonary bypass, 1 g was added to the priming solution. In 35 patients with a normal estimated creatinine clearance (CLcr) ≥50 ml/min, a free cefazolin concentration <4 µg/ml was observed in 11.4, 5.7 and 54.3% of patients before the second dose, at the end and 24 h after operation, respectively. In contrast, only 7.4% of 27 patients with CLcr <49 ml/min had a free cefazolin concentration <4 µg/ml 24 h after the operation. There was a high negative correlation between CLcr and time above the target minimal inhibitory concentration (MIC) when the CLcr was <50 ml/min (r(2) = 0.807), and no correlation when the CLcr was ≥50 ml/min. Renal function has a significant impact on the PK-PD of prophylactic cefazolin in cardiothoracic surgery. The postoperative drug dosing intervals should be <6 h in order to achieve a 100% time above the MIC in patients with CLcr ≥ 50 ml/min.

[Off-pump coronary artery bypass grafting; its impact on renal function].

PURPOSE: We evaluated the impact of off-pump coronary artery bypass grafting (off-pump CABG: OPCAB) on the perioperative renal function. METHODS: Isolated CABG was performed on 359 patients during the period from January 1999 to September 2002. Nine patients on dialysis were excluded from this study and 350 patients were divided into 2 groups: OPCAB Group (n = 214) and on-pump Group (n = 136). Perioperative serum CRE levels of the 2 groups were compared. RESULTS: The ratio of patients with renal impairment (CRE > 1.5 mg/dl) in the OPCAB Group was 8%, which did not differ statistically from that of the on-pump Group (4%). Patients who had renal impairment postoperatively accounted for 20% of the OPCAB Group, which did not differ from that of the on-pump Group (18%). The postoperative CRE/preoperative CRE ratio was lower in the OPCAB Group (1.28) than that of the on-pump Group (1.44). CONCLUSION: The renal function was preserved in the OPCAB Group compared to the on-pump Group.

Hyperthyroidism causes mechanical insufficiency of myocardium with possibly increased SR Ca2+-ATPase activity.

Hyperthyroidism is known to affect multiple organ functions, and thyroid hormone has been known to improve myocardial function in a failing heart. The purpose of this study is to elucidate the functional and metabolic effects of thyroid hormone on myocardium in a rat model exposed to long-term excess thyroid hormone, particularly focusing on the SR Ca(2+)-ATPase (SERCA2) function. 3,5,3'-Triiodo-L-thyronine (T3), or the vehicle, was subcutaneously given for 4 weeks (T3 and control [C] group). Bolus I.V. Thapsigargin (TG) was used to test the SERCA2 function (C-TG and T3-TG) in Langendorff perfused heart. Myocardial functions such as LV-developed pressure (LVDP; mmHg), +/- dP/dt (mmHg/s), tau (ms), and oxygen consumption (MVO(2); ml/min/g wt) were measured. SERCA2 and GLUT4 protein level were also evaluated by Western immunoblotting. Left ventricle to body weight (LV/BW) ratio was significantly higher in the T3 group. Both negative dP/dt and tau were significantly decreased by TG. It is interesting that the decrement of negative dP/dt and tau attained by TG was significantly larger in the hyperthyroid group (T3-TG) than in a normal heart (C-TG). SERCA2 and GLUT4 protein levels were not significantly different between control and the T3 group. We conclude that prolonged exposure to thyroid hormone causes hypertrophy of the myocardium and an augmentation of the SR Ca(2+) ATPase activity. Care must be taken in hyperthyroid heart during the ischemia-reperfusion process where the SRECA2 function is inhibited.

Ascending aortic cannulation via left thoracotomy for distal aortic arch aneurysm operation.

We have cannulated the ascending aorta for cardiopulmonary bypass via left thoracotomy in order to avoid conventional retrograde perfusion from the femoral arteries, which is associated with an increased risk of cerebral embolism. We use silk sutures to retract the anterior margin of the opened pericardium from the chest wall, which provides good exposure and easy control of the ascending aorta. Between July 1997 and November 2000, cannulation proved easy to do and reliable in 24 serial patients.

Arch-first reconstruction via median sternotomy. Short retrograde cerebral perfusion.

In December 1998, we introduced arch-first reconstruction for total aortic arch replacement via conventional median sternotomy in order to shorten the duration of retrograde cerebral perfusion (RCP). We used a separate straight graft for an elephant trunk, which allowed an easy subsequent distal anastomosis. The average RCP duration in this series was 32.1+/-5.8 min (mean+/-SD, range, 24-40 min, n=12), which was significantly shorter (p<0.05) than that of the conventional procedure (45.6+/-12.4 min, range, 34-65 min, n=8), in which we first perform a distal anastomosis. No significant differences in cardiopulmonary bypass time (268+/-81 min vs 258+/-42 min) nor operation time (518+/-213 min vs 517+/-82 min) between the two groups were observed. There was no hospital death in either group. One patient in the second series (conventional method) suffered temporary neurological disturbance. For acceptable RCP duration, total aortic arch replacement is currently the standard procedure in our institution for Stanford A type aortic dissection.

Left ventricular apex venting during deep hypothermia in a case of difficult re-entry into the mediastinum.

The cardiopulmonary bypass techniques of peripheral cannulations and deep hypothermia provide safe and controlled re-entry into the mediastinum, when the thoracic organs are contiguous with the sternum. In such cases, in order to prevent ventricular distention during cooling, left ventricular venting is very important but can be difficult. We made a small (3 cm) left-sided thoracotomy incision and inserted a left ventricular apical venting tube while cooling a patient with a large pseudoaneurysm of the ascending aorta, which was diagnosed 12 years after aortic valve replacement. We found that this technique was easy, safe, and useful to prevent ventricular distention during cooling.

[Indications and results of aortic valve repair].

With the development of prosthetic valves with excellent hemodynamics and durability, aortic valve replacement has become the first choice in the surgical treatment of valve disease. The significant improvement in mortality rates after open-heart surgery has resulted in a demand not only for good hemodynamics but also for a better postoperative quality of life. Because mechanical prosthetic valves are associated with postoperative complications and patients receiving them must remain on anticoagulant therapy for life, and bioprosthetic valves are not sufficiently durable, valve repair techniques are being reevaluated and new ones developed. The indications for valve repair have been extended in mitral valve disease due to the decreased incidence of rheumatic valve disease and increase in degenerative tissue valve disease. Reports indicate that both acute and long-term postoperative results are superior after valve repair compared with valve replacement. Similarly, although some reports on the results of aortic valve repair indicate that the standard techniques do not yield satisfactory long-term results, others suggest that newer techniques may improve the results in both the acute and long-term, chronic phase.

Repair of partial anomalous pulmonary venous connection with a minimal atriotomy.

We present an alternative surgical technique for the repair of a partial anomalous pulmonary venous connection to the higher segment of the superior vena cava. Although the atriotomy is limited in this technique, a sufficiently large systemic venous chamber overlapping to the outside of the superior vena cava can be created.

[Anesthetic management of a patient with mitochondrial encephalomyopathy].

A 46-year-old female with mitochondrial encephalomyopathy underwent the replacement of right femur head under continuous epidural anesthesia. Considering that this disease is a neuromuscular disorder, general anesthesia should be avoided. In addition, the patients with mitochondrial encephalomyopathy tend to show increased concentrations of lactate and pyruvate caused by perioperative stress. Use of lactated Ringer's solution may elevate these concentrations. We managed this patient uneventfully with continuous epidural anesthesia and the use of acetated Ringer's solution during the perioperative period. We consider that continuous epidural anesthesia is useful for a patient with mitochondrial encephalomyopathy.

[Heart rate reduction using edrophonium during coronary artery bypass grafting without cardiopulmonary bypass].

Coronary artery bypass grafting without the use of cardiopulmonary bypass (CPB) is performed with increasing frequency. Performing revascularization on a beating heart is technically more demanding than performing revascularization on the arrested heart, especially in high-risk patients. beta-Blockers and calcium-channel antagonists have been used for the reduction of heart rate (HR) for the local immobilization of the anastomotic site. However, their negative inotropic actions often lead to serious hypotension. Therefore, we investigated the effect of edrophonium on HR reduction in high-risk patients undergoing CABG without CPB. Ten high-risk patients undergoing CABG without CPB were selected. To reduce HR during anastomosis, edrophonium was administered during the procedure. Systemic blood pressure (sBP), HR, and cardiac index (CI) were measured from the induction of anesthesia to the end of surgery. All surgeries were successfully performed without serious complications. To keep the rate under 60 bpm, edrophonium was administered at the time of anastomosis and this decreased the cardiac index from 2.19 to 1.95, while the sPB was maintained easily over 90 mmHg with the infusion of methoxamine. Edrophonium may be useful for the reduction of HR during coronary anastomosis in high-risk patients undergoing CABG without CPB.

[Simultaneous MIDCAB and subtotal gastrectomy in an elderly patient with severe ischemic heart disease].

An 81 year old man with severe ischemic heart disease and left ventricular dysfunction was scheduled for a subtotal gastrectomy for his advanced gastric cancer. His cardiac function was so poor that we performed minimally invasive coronary artery bypass grafting (MIDCAB; coronary artery bypass grafting without cardiopulmonary bypass for LAD through a small left thoracotomy), just before the abdominal operation. Anesthesia was induced and maintained with fentanyl, vecuronium and sevoflurane. To control heart rate below 60 bpm during local coronary occlusion for bypass grafting, edrophonium 5 mg was administered just before the occlusion. During the bypass grafting procedure, the patient's heart rate was maintained at 50-60 bpm and his hemodynamic profile slightly declined but was permissible. After bypass grafting, his cardiac performance was improved with low dose dobutamine. Subsequently subtotal gastrectomy was carried out. His postoperative course was uneventful. Combined MIDCAB and abdominal operation may be beneficial for selected patients with severe ischemic heart disease.

The effect of halothane and sevoflurane on fatigue-induced changes in hamster diaphragmatic contractility.

UNLABELLED: The purpose of this study was to examine the effect of halothane and sevoflurane on fatigue-induced changes in diaphragmatic contractility. Forty-two hamster diaphragm strips were randomly allocated according to anesthetics (no anesthesia control, 1%-3% halothane, 2%-6% sevoflurane) and stimulated directly in an organ bath. Under the influence of the anesthetics, muscle fatigue was induced by repetitive tetanic contraction, and diaphragmatic contractilities (i.e., peak twitch and tetanic tension, twitch contraction time, and half-relaxation time) were measured before and after fatigue. Neither halothane nor sevoflurane changed tension generation before or after fatigue, but each anesthetic significantly enhanced fatigue-induced prolongations of the contraction time and half-relaxation time after fatigue. Specifically, the half-relaxation times after fatigue in the 3% halothane, 4% sevoflurane, and 6% sevoflurane groups (225.6 +/- 37.6, 236.0 +/- 76.5, and 287.3 +/- 55.5 ms, respectively) were more than twice as long as those of the control group (104.7 +/- 19.7 ms, P < 0.05). We conclude that halothane and sevoflurane augment fatigue-induced prolongations of the contraction and relaxation times. Diaphragmatic function may deteriorate when there is a fatiguing task during the clinical administration of halothane or sevoflurane anesthesia. IMPLICATIONS: This study implicates diaphragmatic fatigue during anesthesia. An in vitro hamster diaphragm muscle preparation was used to study the effect of halothane and sevoflurane on fatigue-induced change in contractility. Our findings suggest that increased load on the diaphragm during volatile anesthesia may lead to impaired diaphragmatic contractility.

The membrane-located osmosensory kinase, EnvZ, that contains a leucine zipper-like motif functions as a dimer in Escherichia coli.

The Escherichia coli EnvZ protein is a membrane-located osmosensor, which is a typical member of histidine kinases involved in His-Asp phosphotransfer signaling. We found that EnvZ has a leucine zipper-like motif in its presumed periplasmic domain. The functional importance of this leucine zipper-like sequence was assessed by introducing a number of appropriate amino acid substitutions. The results collectively suggest that certain leucine residues in the leucine zipper-like structure play an important role in the osmotic signal transduction mediated by EnvZ. When cysteine was substituted for the crucial leucine residues, the EnvZ dimer with disulfide bridge was detected in the cytoplasmic membrane. It was thus demonstrated that the EnvZ osmosensor exists and exerts its signaling ability as a dimer.

Altered expression of troponin T isoforms in mild left ventricular hypertrophy in the rabbit.

Alterations in troponin T (TnT) isoforms have been reported in severe human and experimental heart failure (HF), and may play a role in the depressed myofibrillar ATPase activity observed in this condition. It is unclear whether these alterations reflect very severe hemodynamic derangement or are a component of mild hypertrophic stress. Therefore, we studied the expression of TnT isoforms (SDS-PAGE, Western blots), myosin isoforms, myofibrillar ATPase activity, and left ventricular (LV) mechanoenergetics (rbc perfused, isovolumically contracting isolated heart) in a rabbit model of mild hypertrophy (LVH) due to gradual hypertension caused by 12 weeks of cellophane wrap of the kidneys (n=12). LV/body weight ratio increased by 28% in LVH compared to shams (P<0.001); no animals had evidence of HF. In LVH, the percentage of TnT2 was modestly but significantly increased compared to shams [6.2+/-1.9 (+/-S.D. ) v 3.7+/-1.0%, P<0.05], mainly as a consequence of a parallel decrease in TnT4 (P=0.07). Sham hearts ranged from 75-100% V3 isomyosin, whereas all LVH hearts had 100% of the V3 form. There were no significant differences in myofibrillar ATPase activity or mechanical variables, including contraction and relaxation rates. The slope of the VO2-pressure-volume-area relation (a measure of the energy conversion efficiency of the contractile machinery) was also unchanged. We conclude that in the rabbit, shifts in TnT isoforms toward a more "fetal" pattern occur during mild LVH and, therefore, are likely to be a general feature of the response to hemodynamic stress, rather than a phenomenon confined to end-stage disease. These modest shifts are not associated with major alterations in LV myofibrillar ATPase activity or mechanoenergetics.