A study of platelet activation during human cardiopulmonary bypass and the effect of S-nitrosoglutathione.

Cardiac surgery is complicated by the occurrence of post-operative bleeding due to platelet dysfunction. This is largely caused by platelet activation and consumption during cardiopulmonary bypass. Patients undergoing cardiac surgery requiring cardiopulmonary bypass were studied to determine whether early platelet changes due to bypass could be inhibited using the platelet-selective nitric oxide donor S-nitrosoglutathione (GSNO). Flow cytometry was used to measure platelet surface expression of P-selectin (an alpha-granule protein) and glycoproteins (GP) IIb/IIIa and Ib (mediators of aggregation and adhesion) before and 5 and 10 min after commencing cardiopulmonary bypass, in 6 controls and 6 patients receiving GSNO 50 microg/min. Platelet P-selectin expression increased during bypass both in controls and patients receiving GSNO. Glycoproteins IIb/IIIa and Ib fell during bypass in control and GSNO-treated patients. There was no difference between control and GSNO-treated groups. Thus no significant platelet inhibition by S-nitrosoglutathione was demonstrated under these conditions.

S-nitrosoglutathione inhibits platelet activation and deposition in coronary artery saphenous vein grafts in vitro and in vivo.

OBJECTIVE: To investigate platelet activation and deposition in human saphenous vein and internal mammary artery grafts following coronary artery bypass in vitro and in vivo, as well as inhibition of activation by the platelet selective nitric oxide donor S-nitrosoglutathione (GSNO). DESIGN: Controlled in vitro and in vivo studies. SETTING: Tertiary cardiac centre. PATIENTS: 24 patients undergoing coronary artery bypass surgery requiring vein and artery grafts. INTERVENTIONS: In vitro: human platelet rich plasma was perfused through segments of vein and artery, with or without GSNO 10(-6) M, and the platelet count was measured in the effluent. In vivo: indium-111 labelled antibody against the platelet alpha granule protein GMP-140 was injected at the end of coronary bypass grafting and gamma counts were compared between vein and artery grafts with or without systemic infusion of GSNO (40 nmol/min). RESULTS: In vitro: platelet count in perfused vein (< 70% of baseline) decreased more than in artery segments (89-94% of baseline) (p < 0.001). The platelet count was unchanged with GSNO in vein and artery segments. In vivo: gamma counts were greater at all time points over vein than artery grafts (p < 0.05), and were reduced by infusion of GSNO (p < 0.05). CONCLUSIONS: Platelet activation is greater in vein than in artery grafts in vitro and in vivo. Activation, which contributes to early vein graft failure, was inhibited by GSNO.

Neo-intimal development on textured biomaterial surfaces during clinical use of an implantable left ventricular assist device.

Implantable left ventricular assist systems are being developed for long term clinical use. Prototype devices are currently used as extended mechanical bridges to cardiac transplantation. The Thermo Cardiosystems Inc. (TCI) pneumatic pusher plate left ventricular assist device (LVAD) features textured blood contacting surfaces to encourage the formation of an adherent fibrin-cellular coagulum. This serves as the foundation for the development of a neo-intimal lining. The TCI LVAD was implanted in 6 male patients (age range 22-53 years) between 1986 and 1988. The duration of implantation ranged from 1-41 days. No clinical thromboembolic events or pump-related thromboembolism occurred and none was evident at necropsy. The six device linings have been fully evaluated. Explanted devices were free of thrombus and calcification. Lining samples for light and electron microscopy were collected from areas of the diaphragm identical for flex and blood shear conditions and from high and low shear areas on the static housing. Islands of collagenous tissue were deposited on the static housing amongst compact fibrin. By day 13, cells populated the surface of the developing neo-intima overlying the diaphragm. By 41 days, the surface cell density increased and the cells became spindle shaped and relatively orientated in the high shear/flex area. Immunohistochemical techniques suggest that these cells are of mesenchymal origin. Textured blood contacting surfaces appear satisfactory in the preliminary clinical use of this device.

The use of an implantable left ventricular assist device following irreversible ventricular fibrillation secondary to massive myocardial infarction.

A TCI1 rough surface left ventricular assist device (LVAD) was implanted in a 47-year-old man who had sustained a recent massive myocardial infarction complicated by ventricular failure which remained unresponsive to intra-aortic balloon pump therapy and which was further complicated by irreversible ventricular fibrillation. Following implantation of the device and while awaiting a suitable donor organ for transplantation, further extension of the previous infarct resulted in left ventricular rupture and massive haemorrhage which led to his death. We report the successful use of the device in providing haemodynamic support, but caution against inordinate delay in bridging to transplantation patients who are at risk of extension of infarction.

In vitro evaluation of an implantable left ventricular assist device.

The development of implantable left ventricular assist devices (LVADs) has almost reached the stage of providing permanent circulatory support in patients who are unsuitable for, or denied, the transplant option. As part of our ongoing haemodynamic evaluation of the Thermo Cardiosystems Inc. (Boston, USA) Mark 14 pneumatic LVAD, pressure-volume loops have been produced from in vitro studies using a modified National Heart Lung and Blood Institute (NHLBI, USA) mock circulatory loop. These studies have demonstrated that during certain phases of the pump cycle non-physiologically high and low pressures are generated within the LVAD. Such abnormal pressures may damage either the bioprosthetic valves in the LVAD or the native heart, and may have adverse effects on cardiovascular control mechanisms.

Troponin T release with warm and cold cardioplegia.

Cardiac troponin T (cTnT) levels were measured in 41 patients undergoing elective coronary artery surgery. Twenty-one patients received continuous warm antegrade blood cardioplegia to maintain asystole whilst 20 patients received antegrade cold blood cardioplegia intermittently. Serum levels of cTnT were determined preoperatively and at 0, 6, 12 and 18 h postbypass. Peak cTnT levels and total cTnT release (calculated from the area under the curve postoperatively) were found to be significantly higher (p < 0.05: Mann-Whitney) when cold cardioplegic solutions were used. Continuous warm cardioplegia results in lower cTnT release than intermittent cold blood cardioplegia suggesting that the former may provide better myocardial preservation.

An ambulatory, intermediate term left ventricular assist device.

A portable, percutaneous, battery-operated left ventricular assist device intended for intermediate and long-term use is described. The system performed satisfactorily in vitro for periods of up to 9 months and in vivo for periods in excess of 3 months. Long-standing hypertension was observed in a 98 day implant with accompanying renal and visceral vascular changes. No evidence of peripheral thromboembolism was seen. Examination of the textured blood pump surface revealed an established biologic lining, characteristic of that previously seen in calves with some evidence of peripheral calcification.