Gabapentin Activates Spinal Noradrenergic Activity in Rats and Humans and Reduces Hypersensitivity after Surgery

Background: Gabapentin has been reported to inhibit various acute and chronic pain conditions in animals and humans. Although the efficacy of gabapentin depends on the [alpha]2[delta] subunit of voltage-gated calcium channels, its analgesic mechanisms in vivo are still unknown. Here, the authors tested the role of spinal noradrenergic inhibition in gabapentin's analgesia for postoperative pain.

Methods: Gabapentin was administered orally and intracerebroventricularly to rats on the day after paw incision, and withdrawal threshold to paw pressure was measured. The authors also measured cerebrospinal fluid concentration of norepinephrine and postoperative morphine use after surgery in patients who received oral placebo or gabapentin.

Results: Both oral and intracerebroventricular gabapentin attenuated postoperative hypersensitivity in rats in a dose-dependent manner. This effect of gabapentin was blocked by intrathecal administration of the [alpha]2-adrenergic receptor antagonist idazoxan and the G protein-coupled inwardly rectifying potassium channel antagonist tertiapin-Q, but not by atropine. In humans, preoperative gabapentin, 1,200 mg, significantly increased norepinephrine concentration in cerebrospinal fluid and decreased morphine requirements.     

Adding Bupivacaine to High-potassium Cardioplegia Improves Function and Reduces Cellular Damage of Rat Isolated Hearts after Prolonged, Cold Storage

Background: Bupivacaine retards myocardial acidosis during ischemia. The authors measured function of rat isolated hearts after prolonged storage to determine whether bupivacaine improves cardiac protection compared with standard cardioplegia alone.

Methods: After measuring cardiac function on a Langendorff apparatus, hearts were perfused with cardioplegia alone (controls), cardioplegia containing 500 [mu]m bupivacaine, or cardioplegia containing 2 mm lidocaine; were stored at 4[degrees]C for 12 h; and were then reperfused. Heart rate and left ventricular developed pressures were measured for 60 min. Maximum positive rate of change in ventricular pressure, oxygen consumption, and lactate dehydrogenase release were also measured.

Results: All bupivacaine-treated, four of five lidocaine-treated, and no control hearts beat throughout the 60-min recovery period. Mean values of heart rate, left ventricular developed pressure, maximum positive rate of change in ventricular pressure, rate-pressure product, and efficiency in bupivacaine-treated hearts exceeded those of the control group (P < 0.001 at 60 min for all). Mean values of the lidocaine group were intermediate. Oxygen consumption of the control group exceeded the other groups early in recovery, but not at later times. Lactate dehydrogenase release from the bupivacaine group was less than that from the control group (P < 0.001) but did not differ from baseline.     

Minimally Invasive Coronary Artery Bypass Grafting: A New Method Using an Anterior Mediastinotomy

The benefit of internal mammary artery (IMA) grafting as a long-lasting intervention for coronary artery disease is well recognized. However, largely because they are less invasive, catheter based alternatives are frequently chosen, particularly to treat single or double vessel disease. To retain the advantages of the IMA graft, and to offset the invasiveness of conventional coronary artery bypass grafting, we developed a new minimally invasive method using an anterior mediastinotomy for treating left anterior descending (LAD) or right coronary artery disease, or both. Feasibility studies using 16 pigs and a human cadaver led to approval by the Institutional Review Board for use of this procedure to treat six patients (four men, two women; mean age, 63.8 ± 13.6 [SD] yrs) who granted informed consent. Pedicle dissection of the IMA, using video assisted thoracoscopy if necessary, was made through a 2-to 3-inch horizontal anterior mediastinotomy. The underlying LAD artery was grafted during femoral vessel cardiopulmonary bypass, with cooling to 30°C, induced ventricular fibrillation, and left ventricular venting if required. Transesophageal echocardiography performed after bypass showed that two patients maintained normal wall motion and four had improvement from the original impairment. One patient suffered a recurrence of angina 4 weeks after the procedure; recatheterization showed an acutely angled IMA, subsequently corrected by balloon angioplasty. The results of follow-up dobutamine echocardiographic stress tests were negative in all patients. With this minimally invasive approach, the procedure should provide the benefits of IMA grafting with shorter hospital stay, more rapid recovery, and less overall cost.