Coronary Porcine Research Articles

Long‐term impact of balloon postdilatation on neointimal formation: An experimental comparative study between second‐generation self‐expanding versus balloon‐expandable stent technologies

Background: Self-expanding stents (SES) are reemerging as therapeutic alternatives to treat coronary artery disease. It has been proposed that SES can improve clinical outcomes by inducing less injury at implantation and achieving better vessel wall apposition.To date, little data exists comparing the vascular response to both methods of deployment in a controlled experimental setting. Objective: To quantify differences in vascular injury and healing between second-generation SES and balloon-expandable stents (BES) and the effects of balloon post-dilatation in a porcine coronary model. Methods: Seventy-five bare SES (AXXESS or vProtect) and 42 BES (Vision) were implanted in porcine coronaries. A subset of these received balloon post-dilatation(SES 1 D 5 22, BES 1 D 5 20). Follow-up was scheduled at 30 (BES 5 10, BES 1 D 56, SES 5 19, SES 1 D 5 8), 90 (BES 5 6, BES 1 D 5 8, SES 5 19, SES 1 D 5 8), and 180 days (BES 5 6, BES 1 D 5 6, SES 5 15, SES 1 D 5 6). Results: In vivo imaging and histological analysis showed that neointimal formation peaks early (30 days) in BES. Conversely, for SES, the peak occurred later (90 days). However, the neointimal formation achieved in either group equalized at 180 days. For SES, post-dilatation shortened the peak of neointimal formation to 30 days. Conversely, for BES, post-dilatation delayed the peak of neointimal formation to 90 days. At 30 days, histology showed that SES had significantly less injury. However, at 90 days, injury scores tended to be higher for SES. By 180 days, injury scores were comparable between both groups. Conclusions: The mechanism of stent expansion influences the degree of vascular injury and healing. The synergistic use of balloon post dilatation changes the dynamics of healing and may impact the potential beneficial effects inherent to SES technologies.

Specific Coronary Drug-Eluting Stents Interfere With Distal Microvascular Function After Single Stent Implantation in Pigs

The aim of this study was to compare the effects of single drug-eluting stents (DES) on porcine coronary function distal to the stent in vivo and in vitro. The mechanism of endothelial dysfunction occurring in human coronary conduit arteries up to 9 months after DES implantation is unknown. A sirolimus-eluting stent (SES), paclitaxel-eluting stent (PES), and a bare-metal stent (BMS) were implanted in the 3 coronary arteries of 11 pigs. After 5 weeks, in vivo responses in distal coronary flow to different doses of bradykinin (BK) and nitrates were measured. In vitro, vasodilation to BK and nitrates, as well as vasoconstriction to endothelin (ET)-1 were assessed in both distal coronary conduit and small arteries. In addition, contributions of nitric oxide (NO) and endothelium-derived hyperpolarizing factors (EDHFs) and cyclic guanosine monophosphate (cGMP) responses to BK-stimulation were determined in vitro. Both DES did not alter in vivo distal vasomotion. In vitro distal conduit and small arterial responses to BK were also unaltered; DES did not alter the BK-induced increase in cGMP. However, after NO synthase blockade, PES showed a reduced BK-response in distal small arteries as compared with BMS and SES (p < 0.05). The ET-1-induced vasoconstriction and vascular smooth muscle cell function were unaltered. In this study of single stenting in healthy porcine coronaries for 5 weeks, SES did not affect distal coronary vascular function, whereas PES altered distal endothelial function of small arteries under conditions of reduced NO bioavailability. Therefore, specifically the EDHF component of microvascular function seems affected by PES.

Serial imaging and histology illustrating the degradation of a bioabsorbable magnesium stent in a porcine coronary artery

Magnesium alloy stents have demonstrated swift degradation within 90 days of implantation in porcine and human coronary arteries. These stents are radiolucent and thus cannot be visualized by angiography. To assess the rate of degradation, bioabsorbable magnesium alloy stents were deployed in porcine coronaries, and serial imaging by intravascular ultrasound (IVUS) (Panels A and B) and optical coherence tomography (OCT) (Panels C and …

12-lipoxygenase in porcine coronary microcirculation: implications for coronary vasoregulation.

Noncyclooxygenase metabolites of arachidonic acid (AA) have been proposed to mediate endothelium-dependent vasodilation in the coronary microcirculation. Therefore, we examined the formation and bioactivity of AA metabolites in porcine coronary (PC) microvascular endothelial cells and microvessels, respectively. The major noncyclooxygenase metabolite produced by microvascular endothelial cells was 12(S)-hydroxyeicosatetraenoic acid (HETE), a lipoxygenase product. 12(S)-HETE release was markedly increased by pretreatment with 13(S)-hydroperoxyoctadecadienoic acid but not by the reduced congener 13(S)-hydroxyoctadecadienoic acid, suggesting oxidative upregulation of 12(S)-HETE output. 12(S)-HETE produced potent relaxation and hyperpolarization of PC microvessels (EC(50), expressed as -log[M] = 13.5 +/- 0.5). Moreover, 12(S)-HETE potently activated large-conductance Ca(2+)-activated K(+) currents in PC microvascular smooth muscle cells. In contrast, 12(S)-HETE was not a major product of conduit PC endothelial AA metabolism and did not exhibit potent bioactivity in conduit PC arteries. We suggest that, in the coronary microcirculation, 12(S)-HETE can function as a potent hyperpolarizing vasodilator that may contribute to endothelium-dependent relaxation, particularly in the setting of oxidative stress.

Vascular repair after balloon overstretch injury in porcine model effects of intracoronary radiation

OBJECTIVESThe purpose of this study was to evaluate the effect of IR on thrombus formation and dissection repair following overstretch balloon injury in porcine coronary arteries.BACKGROUNDExposure of blood to the injured arterial wall after percutaneous transluminal coronary angioplasty (PTCA) induces thrombus formation and inflammation in the dissection plane. Neointima formation is related to smooth muscle cell (SMC) proliferation and migration into the preformed thrombus. Intracoronary radiation (IR) with doses of 10 to 25 Gy using either beta or gamma emitters can prevent neointima accumulation by reducing SMC proliferation. However, there are some indications that IR may delay the process of dissection repair after PTCA. The purpose of this study was to evaluate the effect of IR on thrombus formation and dissection repair after overstretch balloon injury in porcine coronary arteries.METHODSForty porcine coronaries were injured by balloon overstretch followed by either 0 or 18 Gy of 90Y prescribed to 1.2 mm from the balloon center. The animals were euthanized 14 days after treatment, and intimal area (IA) and IA corrected for medial fracture length (IA/FL) were quantified by digital image analysis. Dissections were quantified by tracing the length, thickness and area behind the dissection flap. The rate of dissections was calculated for each group. Thrombi were identified and designated as intraluminal thrombus or thrombus within dissection planes (mural thrombus), and area measurements were obtained.RESULTSThe irradiated group showed a significant reduction of IA/FL (0.55 ± 0.29 vs. 0.05 ± 0.09; p < 0.001). No difference was observed in the rate of dissection between control and irradiated arteries (77% vs. 88%, respectively). The control group showed a smaller dissection area (0.19 ± 0.28 mm2 vs. 0.32 ± 0.29 mm2; p < 0.05) with smaller mural thrombi (0.03 ± 0.01 mm2 vs. 0.29 ± 0.30 mm2; p < 0.001). A strong correlation between dissection area and neointima area was observed only in the control group (R2 = 0.474; p < 0.003; alpha0.05 = 0.862). A positive correlation between mural thrombus and dissection area was observed only in the irradiated group (R2 = 0.889; p < 0.001; alpha0.05 = 1.00).CONCLUSIONSThese results suggest that the dissection area may be a useful parameter by which to quantify the extent of injury and repair after IR and may indicate an incomplete healing process after IR at this time point.