A comparison of the microvascular response in the healing wound in the spontaneously hypertensive and non-hypertensive rat.

BACKGROUND

In the Spontaneously Hypertensive Rat (SHR), there is a significantly greater blood flow at the paw but not at the back than in the non-hypertensive Wistar Kyoto (WKY) rat. We wanted to assess the effect of this higher blood flow on wound healing at the paw.

MATERIALS AND METHODS

We characterized the microvascular composition of wounds at the back and paw of 9 SHR rats and 10 WKY rats using a quantitative imaging program. Blood flow was compared using laser Doppler technology.

RESULTS

The blood flow response to wounding at the back was identical in the SHR and WKY rats. There was an immediate sharp increase in flow at the center of the wound. Blood flow reached a peak at 3 days and then decreased somewhat by day 7, but still remained five-fold higher than the prewound baseline values. There was also a two-fold increase at the back wound perimeter. There were no differences in microvascular composition at the back between the SHR and WKY rats. In contrast, there was an immediate enormous increase in blood flow at paw wound center in the SHR rats. Flow increased to 75 ml/min/100 gm by 24 h then fell back sharply. Blood flow at the paw in the WKY rats changed very little over the 7 days post wounding. At 3 days, the flow was about twice as high in the SHR than in the WKY wound, but, by day 7, flow was similar in the two rat strains. At the SHR wound perimeter, there was a small increase in flow which was sustained through day 7. Although the microvascular composition at the paw wound center was similar in the SHR and WKY rats, there was a notable difference at the paw perimeter. At baseline, there was a slightly greater capillary density in the SHR paw (32 +/- 1 per mm3) than the WKY paw (25 +/- 8 per mm3). At 7 days after wounding, there was a substantial increase in capillary number in the SHR rats (48 +/- 8 per mm3) as compared to baseline (p = 0.05). In contrast, there was no significant difference in capillary number in the WKY paw wound perimeter (20 +/- 3 per mm3) as compared to baseline.

CONCLUSIONS

There is a substantial difference in wound blood flow response between the hypertensive and the non-hypertensive rat. At the back, the blood flow effects of wounding are similar, but, at the paw, the SHR rat shows a dramatic transient increase in flow in the early phases of wound healing. There is apparently no capability to upmodulate microvascular resistance in response to increased pressure at this early stage of wound healing. However, within several days, the granulation tissue microvasculature becomes capable of controlling the effects of raised pressure in the SHR rat. In the SHR paw wound perimeter, there are significantly more capillaries than in the WKY rat. It is possible that greater capillary proliferation in the SHR rat results from higher blood flow in the early phase of wounding. The contrast between the WKY rat and the SHR rat serves to further illustrate the complexity of blood flow regulation which occurs during wound healing.