This study shows that C. pneumoniae infection enhances the inflammatory process by increasing T-lymphocytes in the plaque and accelerates the formation of complex lesions.

These observations demonstrate that vessel growth, predominantly in the region adjacent to the infarcted zone, results in complete normalization of coronary vasodilatory capacity within 35 days after MI.

An increase in aortic wall mass resulting from chronic infusion of angiotensin II does not alter the dynamic compliance of the vessel under isobaric conditions.

Objectives: Cardiac remodeling due to myocardial infarction (MI) includes myocyte hypertrophy, collagen deposition, a rise in DNA synthesis, and normalization of initially diminished maximal coronary bloodflow. Previously, we demonstrated that early captopril treatment can prevent the rise in total DNA synthesis, collagen deposition and hypertrophy. In the present experiments, we investigated the effects of captopril or perindoprilat treatment on cardiac endothelial cell proliferation and maximal coronary flow. Methods: MI was induced by ligation of the left coronary artery in Wistar rats. Sham-operated and infarcted rats were treated with captopril (12 mg / kg.d s.c.) from either day 0-21 (early) or day 21-35 (late) after surgery. In isolated retrogradely perfused rat hearts, maximal coronary flow was determined following maximal dilatation with nitroprusside and adenosine (1 mM each). In separate groups, sections of hearts of sham-operated and MI rats treated with BrdU (day 7-14) and either captopril or perindoprilat (1 mg / kg.d s.c.; day 0-14) were double stained with a monoclonal anti-BrdU antibody and the lectin GSI. The total fraction of DNA synthesizing cells and its proportion of endothelial cells was determined. Results: Maximal coronary flow was completely normalized in MI hearts within three weeks after surgery. Early captopril, but not late captopril, inhibited the normalization of maximal coronary flow in MI hearts (Early: sham, 27.461.0; MI, 21.261.4 ml / min; P,0.05; mean6SEM) without affecting the hypertrophic response. The total fraction of DNA synthesizing cells was significantly increased in MI hearts (sham: 7.661.9; MI: 14.962.2%). The proportion of endothelial cells, however, was comparable in sham-operated and infarcted hearts (sham: 3063; MI: 3363%). Both early captopril and perindoprilat treatment inhibited total DNA synthesis in MI hearts. Only in captopril pre-treated hearts, this inhibition was associated with a disproportionate inhibition of the endothelial cell proliferation (10.362.0%). Conclusion: Early captopril treatment inhibits endothelial cell proliferation and coronary vessel growth following MI, which seems to be partly due to inhibition of the renin angiotensin system.

Ischemia activates several compensatory mechanisms to restore blood supply. To investigate possible changes in the reactivity of blood vessels after acute and chronic ischemia of skeletal muscle, the response (resistance changes) of the vascular bed to angiotensin II (AII) and phenylephrine (PE) in a hindlimb perfusion model were studied in control, acutely ischemic (45 min) and chronically ischemic (4 weeks) spontaneously hypertensive rats. Furthermore, the effects of angiotensin I (AI) were studied to investigate the involvement of local angiotensin-I-converting enzyme (ACE) in adaptive responses. Ischemia was induced by partial occlusion of the left common iliac artery. Both in acute and chronic ischemia, the reactivity (maximal resistance change) of the vascular bed in the ischemic hindlimb to AI, AII and PE was increased only in severe ischemia (residual flow < 40%), whereas the sensitivity (ED50) was not influenced. The increase in reactivity was comparable for AI and AII, implying that local ACE seems not to be involved. These results suggest that severe ischemia of skeletal muscle results in nonselective hyperreactivity of the vascular bed, which may be due to alterations of receptor-linked mechanisms or ultrastructural changes of blood vessels.

No abstract

In the present experiments the effect of long-term peripheral ischemia on the capillarity of two hind limb skeletal muscles was investigated in spontaneously hypertensive rats. Furthermore, the effect of antihypertensive therapy on changes in capillarity and on the previously observed hyperreactivity of the ischemic vascular bed to vasoconstrictors was investigated in perfused hind limbs of rats after long-term treatment with the angiotensin I converting enzyme inhibitors captopril (0.5 mg/kg -h) or zabiciprilate (0.025 mg/kg • h), the angiotensin II type 1 receptor antagonist losartan (0.625 mg/kg • h), or the calcium antagonist felodipine (0.042 or 0.42 mg/kg • h). Skeletal muscle ischemia in the left hind limb was induced by partial ligation of the left common iliac artery. Long-term (4 weeks) ischemia increased significantly the capillary-to-fiber ratio in the soleus muscle, composed predominantly of type I fibers in spontaneously hypertensive rats, of the ischemic hind limb, whereas capillarity in the contralateral muscle was not affected. Furthermore, capillarity in the gastrocnemius muscle (type II muscle fiber part) of both the ischemic and contralateral hind limb did not change. Long-term treatment with the angiotensin I converting enzyme inhibitors during ischemia abolished the increase in the capillary-to-fiber ratio in the soleus muscle, whereas a comparable antihypertensive dose of felodipine had no effect. Greater blood pressure reductions by both losartan and felodipine prevented increases in capillarization in skeletal muscle ischemia. With respect to vascular hyperreactivity during ischemia, only treatment with losartan normalized reactivity of the ischemic vascular bed to vasoconstrictors. These data suggest that both the renin-angiotensin system, probably through the angiotensin II type 1 receptor, and hypoperfusion play a role in the adaptation mechanisms after ischemia of skeletal muscle. and metabolic and structural adaptations of skeletal muscles. 3 '' In a rat model for long-term ischemia of skeletal muscle, we previously demonstrated hyperreactivity of the total vascular bed of severely ischemic hind limbs to the vasoconstrictors angiotensin I (Ang I), angiotensin II (Ang II), and phenylephrine, 5 whereas in a comparable ischemia model Verheyen and coworkers observed a hyperreactivity to serotonin 6 and a thromboxane analogue. One of the mechanisms for restoring blood supply to the ischemic regions is the development of collateral vessels. 8 -9 Generation of new vessels has been described in relative hypoxic (increased oxygen demand) and hypoxic situations after endurance training 10 "; similar observations were made after long-term electrical stimulation of skeletal muscles 12 and in ischemia of skeletal

Background Guideline adherence is generally high in Dutch general practices. However, the prescription of insulins to type 2 diabetes mellitus patients is often not in line with the guideline, which recommends NPH insulin as first choice and discourages newer insulins. This qualitative study aimed to identify the reasons why primary care healthcare professionals prescribe insulins that are not recommended in guidelines. Methods Digital focus groups with primary care practitioners were organised. A topic list was developed, based on reasons for preferred insulins obtained from literature and a priori expert discussions. The discussions were video and audio-recorded, transcribed verbatim and coded with a combination of inductive and deductive codes. Codes were categorized into an existing knowledge, attitudes and behaviour model for guideline non-adherence. Results Four focus groups with eleven general practitioners, twelve practice nurses, six pharmacists, four diabetes nurses and two nurse practitioners were organised. The prescription of non-recommended insulins was largely driven by argumentation in the domain of attitudes. Lack of agreement with the guideline was the most prominent category. Most of those perspectives did not reflect disagreement with the guideline recommendations in general, but were about advantages of non-recommended insulins, which led, according to the healthcare professionals, to better applicability of those insulins to specific patients. The belief that guideline-recommended insulins were less effective, positive experience with other insulins and marketing from pharmaceutical companies were also identified as attitude-related barriers to prescribe guideline-recommended insulins. One additional category in the domain of attitudes was identified, namely the lack of uniformity in policy between healthcare professionals in the same practice. Only a small number of external barriers were identified, focusing on patient characteristics that prevented the use of recommended insulins, the availability of contradictory guidelines and other, mostly secondary care, healthcare providers initiating non-recommended insulins. No knowledge-related barriers were identified. Conclusions The prescription of non-recommended insulins in primary care is mostly driven by lack of agreement with the guideline recommendations and different interpretation of evidence. These insights can be used for the development of interventions to stimulate primary care practitioners to prescribe guideline-recommended insulins.