Fifty-three (96%) of 55 patients with coronary artery stenosis were positive for serum anti-HHV-6 IgG, and 50 (91%) of these patients had anti-HHV-7 IgG. The number of cases sero-positive for HHV-6 and -7 in the 54 age matched control volunteers was 52 (96%) and 53 (98%), respectively. No statistical difference in the sero-prevalence of the viruses existed between the patients and the control group. The mean geometric titer (log10) of anti-HHV-6 IgG in both the patients and controls were the same (1.4) (P = 0.845), whereas anti-HHV-7 titers were 1.4 and 1.5, respectively (P = 0.161). Ten (18%) of the 55 patients had anti-HHV-6 IgM; eight (15%) of the 54 control volunteers were also positive (P = 0.636). Three (5%) of the 55 patients had anti-HHV-7 IgM, whereas 3 (6%) of the 54 control volunteers had detectable serum antibody (P = 0.691). Forty-seven of the 55 patients were examined by follow-up angiographic evaluation to clarify the association between viral infection and restenosis following balloon angioplasty. Fifteen of these patients developed restenosis, as determined by angiography. The mean geometric titer (log10) of anti-HHV-6 IgG were 1.3 and 1.4 in patients with restenosis and those without restenosis, respectively (P = 0.724). The mean geometric titer (log10) of anti-HHV-7 IgG in patients with restenosis was not significantly higher (1.5) than in patients without restenosis (1.3) (P = 0.099). Three (20%) of the 15 patients affected by restenosis had anti-HHV-6 IgM; five (16%) of the 32 control patients also had the antibody (P = 0.965). One (7%) of the 15 patients with restenosis and 2 (6%) of the 32 patients without restenosis had anti-HHV-7 IgM (P = 0.558). The present study demonstrates that HHV-6 and -7 reactivation is not associated with the establishment of coronary artery stenosis and restenosis following balloon angioplasty.
Restenosis was studied histopathologically by serial step sectioning of 22 coronary arteries from 21 patients in whom percutaneous transluminal coronary angioplasty (PTCA) had been performed (9 arteries from patients who had died shortly after PTCA and 1 3 from those who had died considerably later). Nine of the 13 arteries from the patients who had died long after PTCA were immunohistochemically stained using anti-actin antibody for examination of spindle-shaped cells proliferating in the intima. In the patients who had died shortly after PTCA, all 9 arteries showed fresh thrombus formation. In the patients who had died considerably later after PTCA, however, there was fragmentation of the internal elastic lamina (IEL) in 9 arteries. In each of these 9 arteries, a remarkable proliferation of intimal cells was observed on the intimal side, mainly at the site of the IEL fragmentation. These spindle-shaped cells were identified as smooth muscle cells (SMC) because they stained reddish-brown with Masson's trichrome, and because immunohistochemical staining with anti-actin antibody was also positive. In 2 arteries, proliferation of SMC and elastic fibers was observed on the luminal side of the intima, despite absence of fragmentation in the IEL. Proliferation of SMC in false lumens was identified in 2 patients with medial dissection . From the above findings, the following 4 forms of restenosis after PTCA have been identified: l. thrombus formation; 2. proliferation of SMC on the intimal side, mainly around fragmentation in the IEL; 3. proliferation of SMC on the luminal side of the intima where there was no fragmentation of the IEL ; and 4. proliferation of SMC in dissected false lumen. The proliferation of SMC on the intimal side of the disrupted IEL was thought to have been a result of migration of SMC from the media to the intima, because SMC proliferation was seen around the disrupted region.
The histological picture of sites of coronary spasms has not yet been made sufficiently clear. A histopathological examination was performed on the coronary artery of a patient who died of acute myocardial infarction after a refractory coronary spasm was identified by coronary arteriography. In the site of the coronary spasm, intimal bleeding as well as infiltration by lymphocytes and plasma cells in the adventitia were seen. In the same region, fracture of intimal collagen fibers and rupture of atheromatous plaque were observed. Although it is very difficult to prove in individual cases of acute myocardial infarction that spasms played a part, some cases involving spasms may possibly exist among the cases of acute myocardial infarction showing atheromatous plaque rupture--thrombus formation.
