Hypertension is a leading cardiovascular risk factor worldwide, playing a significant role in ischemic heart disease, stroke and atherosclerosis. Co-existence of systemic hypertension in patients undergoing infrainguinal bypass surgery was estimated at 70% and 68% of re-intervention cases in coronary artery grafting procedures were reported to be hypertensive. Venous hypertension also leads to chronic vein insufficiency leading to superficial vein incompetence, limiting the availability of autologous vein grafts. Here, we describe development of a hypertensive ovine model that was employed to test the performace of autologous arteries or veins when transplanted under clinically realistic conditions.
Our study involved the development of an ovine renal hypertension model utilizing the 2K1C model, where nephrectomy was performed on the left kidney and renal artery stenosis was performed on the right kidney after 3 weeks. Following the onset of hypertension, carotid artery grafts (CAG) or facial vein grafts (FVG) were implanted into carotid arteries of hypertensive (HT) and normotensive sheep (NT). Autologous carotid artery (CA) was used as a control. In addition, valuable real-time hemodynamic data was collected through instrumentation that was inserted during grafting. The instrumentation included a Doppler flow probe, ultrasonic crystals and in-line pressure catheters to measure flow rate, dynamic changes of graft diameter and arterial pressure.
With the 1K1C model, we were able to achieve elevated systolic as well as diastolic pressures, leading to increased Mean Arterial Pressure (MAP). Our in-vivo hemodynamics data revealed that in hypertensive animals the pulse wave velocity increased and the dynamic radial compliance was significantly reduced, indicating increased stiffness, a hallmark of hypertensive vessels. Surprisingly, both CAG and FVG showed significantly reduced mechanical properties as well as collagen and elastin content following grafting, albeit FVG were affected to a higher extent by HT. Smooth muscle cell remodeling, as well as vascular function was also more significantly affected by HT in FVG as compared to CAG. Interestingly, transplanted FVG into HT animals were infiltrated by pro-inflammatory macrophages, while in NT animals, transplanted FVG were infiltrated mostly by macrophages of an anti-inflammatory phenotype.
We present here a pre-clinical large animal hypertensive model, which allows for real-time hemodynamic data monitoring, to evaluate remodeling and performance of autologous vessels. Our study revealed that autologous arteries lose many of the vascular properties when grafted under NT conditions, but are not affected by HT as much as the veins. On the contrary, grafted veins showed constructive remodeling under NT, while under HT they performed poorly. This data has repercussions in choosing appropriate graftable vessels harvested from patients suffering from hypertension.
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