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Blood pressure measurement in the artery proximal and distal to an intra-arterial embolus during thrombolytic therapy
  1. Takatoshi Sorimachi1,2,
  2. Kenichi Morita1,2,
  3. Yasushi Ito1,
  4. Yukihiko Fujii1
  1. 1Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata, Japan
  2. 2Department of Neurosurgery, Nishiogi-chuo Hospital, Tokyo, Japan
  1. Correspondence to Takatoshi Sorimachi, Department of Neurosurgery, Brain Research Institute, University of Niigata, 1-757, Asahimachidori, Chuo-ku, Niigata, 950-8585 Japan; sorimachi{at}bri.niigata-u.ac.jp

Abstract

Background and aim When a cerebral embolism occurs, pressure gradients in the arteries between sites proximal and distal to the embolus exert hydromechanical forces that push the embolus distally, and potentially affect successful revascularization during clot removal. We investigated the relationships between blood pressures that occur immediately distal and proximal to the embolus, systemic blood pressure and clinical variables.

Methods 36 patients with embolism of the internal carotid artery (13 patients) or the proximal middle cerebral artery (23 patients) were treated using intra-arterial thrombolysis. The mean blood pressure (MBP) at the sites proximal (proximal MBP) and distal (distal MBP) to the embolus was measured with a microcatheter. Simultaneously, the systemic MBP was recorded by cuff measurement.

Results Proximal, distal and systemic MBPs (mean±SD) were 95.2±13.2 mm Hg, 35.9±13.5 mm Hg and 98.2±12.2 mm Hg, respectively. The proximal MBP was significantly higher in the patients with systemic MBP≥100 mm Hg than those with systemic MBP<100 mm Hg (p<0.05). The distal MBP showed no difference between the high and normal systemic MBP groups.

Conclusions Higher systemic blood pressure produced stronger hydromechanical forces on the clot, forming a proximal–distal blood pressure gradient across the clot. The stronger hydromechanical force could result in higher compaction of the clot, thus making it more difficult to remove.

  • Artery
  • cerebral infarction
  • embolic
  • embolism
  • stroke
  • thrombectomy
  • thrombolysis

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Mechanical thrombectomy for acute ischemic stroke caused by large vessel occlusions has been recently shown to significantly restore perfusion and improve clinical outcomes.1–7 Various devices have been employed in mechanical thrombectomy; one principle for clot retrieval involves a combination of moving the clot proximally in the target artery and removing the clot through a catheter.8–11 Pressure gradients in the arteries between sites proximal and distal to the embolus exert hydromechanical forces that push the embolus distally. In the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials, Nogueira et al9 reported that higher blood pressure on presentation is associated with lower revascularization rates. They speculated that the ability to remove the clot is negatively influenced by blood pressure because of the hydraulic forces imposed by a higher blood pressure.9 We obtained two measurements for blood pressure through a microcatheter in the artery, in the regions just proximal and distal to the emboli during intra-arterial thrombolytic therapy for occlusion of a major artery. We reported that the blood pressure distal to the embolus was significantly lower in patients with bad outcomes compared with those with good outcomes.12 To the best of our knowledge, the blood pressure measured in the region proximal to an embolus has never been demonstrated before, and therefore, the hydromechanical force, which is a blood pressure gradient between the proximal and the distal sites to the embolus, has never been confirmed. The effect of an increase in systemic blood pressure on the hydromechanical force that impacts the clot remains unknown.

In this study, we first proved the existence of hydromechanical forces on the embolus by measuring the blood pressure gradient between the regions just proximal and distal to an embolus. We then identified the effect of systemic blood pressure on the hydromechanical forces by analyzing relationships between systemic blood pressure and various clinical variables, including the blood pressures just proximal and distal to the embolus. Lastly, the relationships between clinical outcome, the blood pressures measured just proximal and distal to the embolus, and various clinical variables were evaluated.

Methods

Patient population

Between April 2001 and December 2005, 36 consecutive patients <85 years of age, with sudden onset of both severe hemiparesis and gaze palsy of the hemiparetic side within the previous 6 h were treated with intra-arterial thrombolysis (18 men, 18 women; age range 48–84 years old, mean±SD, 71.6±8.3 years old). All patients suffered from cerebral ischemia caused by major arterial occlusion. In 13 patients the occlusion was of the terminal internal carotid artery (ICA), and in 23, the proximal middle cerebral artery (MCA). Patients' initial neurological status, which was rated using the National Institutes of Health Stroke Scale (NIHSS), ranged from 16 to 28 (mean±SD, 21.6±3.5). CT scanning and MR diffusion-weighted imaging were performed in all patients. Intra-arterial thrombolysis with mechanical disruption using a microcatheter and a guide wire was started between 60 and 360 min (mean±SD, 211±58.4 min) after the onset of symptoms. We previously reported the methodological details of thrombolysis with mechanical disruption.12 13 During this procedure, the blood pressure was measured in intracranial arteries just distal and proximal to the embolus. This study was approved by Nishiogi-chuo Hospital Ethical Committee, and informed consent was obtained from family members.

Blood pressure measurement

A microcatheter (Renegade-18; Boston Scientific Corporation, Natick, Massachusetts, USA) was introduced beyond the embolus. Superselective angiography from the microcatheter was performed to assess the precise site of occlusion and the size of the embolus. Then, the arterial pressure just distal to the embolus (distal blood pressure) was measured by connecting the microcatheter to a pressure transducer (Model DX-312; Nihon Koden Co., Tokyo, Japan) and digital pressure monitor (Model KC-013P; Nihon Koden Co.).12 14 When the distal end of the embolus was located in the M2 portion of the MCA, blood pressure was measured in the M2 supplying mainly to the parietal lobe. The microcatheter was then pulled through the region proximal to the embolus. Superselective angiography was performed to confirm the position of the catheter tip, then the blood pressure just proximal to the embolus (proximal blood pressure) was measured by connecting the microcatheter to the transducer. Simultaneously, systemic blood pressure was also recorded by cuff measurement. The mean blood pressure (MBP) was used in this study.

Evaluation of outcomes

Thrombolytic therapy associated with mechanical disruption, which decreased sizes of emboli and recanalized the occluded arteries, resulted in migration of the emboli into the more distal arteries. Therefore, arteries in which digital subtraction angiography (DSA) showed persistent occlusions were evaluated at the end of thrombolytic therapy. The recanalization state at the end of thrombolytic therapy was grouped into two categories: good recanalization (M3 or more distal occlusion), or insufficient recanalization (occlusion observed in the ICA, M1 or M2).

The outcomes at 1 month after treatment were assessed according to the modified Rankin scale (mRS), a disability scale on which the grades are assigned with reference to the patient's previous lifestyle; these scores ranged from 0 (absence of symptoms) to 5 (bedridden).15 A good outcome was defined as an mRS of ≤2. The first author (T.S.) performed the angiographic and outcome evaluations.

Statistical analyses

Univariate analyses were performed using χ2 analysis and Fisher's exact probability test for categorical variables and the Student t test for continuous variables. Numerical data were expressed as mean±SD. A univariate analysis was performed on each variable to identify possible significant predictors; the variables found to be possibly significant at the p<0.10 level were then included in backward stepwise multivariate logistic regression analysis, which was reduced by successively removing the least significant variable from the model. All variables with p<0.10 were kept in the final model. Analyses resulting in p<0.05 were considered statistically significant. All statistical analyses were performed with StatView 5.0 (SAS Institute Inc.).

Results

All 36 patients underwent blood pressure measurements in the arteries just proximal and distal to the embolus. Proximal, distal and systemic MBPs (mean±SD) were 95.2±13.2 mm Hg, 35.9±13.5 mm Hg and 98.2±12.2 mm Hg, respectively. Both systemic and proximal MBPs were significantly lower than the distal MBPs (p<0.05).

Factors associated with high systemic blood pressure

To investigate variables associated with high systemic blood pressure, systemic MBP was grouped into two categories: normal systemic MBP (<100 mm Hg), or high systemic MBP (≥100 mm Hg) (table 1). The occlusion sites by emboli demonstrated on DSA at the end of the thrombolysis were the M3 or more distal MCA in 32 patients, the M2 in one patient, the M1 in two patients and the ICA in one patient. Therefore, 32 patients belonged to a good recanalization group, and the remaining four patients to an insufficient recanalization group. Univariate analysis was used to compare patient age, sex, time from onset to admission, NIHSS at admission, initial occlusion site on DSA immediately before thrombolysis, proximal MBP, distal MBP and recanalization state at the end of thrombolysis between 24 patients with normal systemic MBP and 12 patients with high systemic MBP. Only proximal MBP had p value <0.10 as measured by univariate analysis. The proximal MBP was included in the logistic regression analysis (table 1). Logistic regression analysis revealed that the proximal MBP remained a significant factor correlated with high systemic MBP (odds ratio (OR), 0.833; p=0.0029).

Table 1

Differences in variables between patients with normal systemic mean blood pressure (<100 mm Hg) and high systemic mean blood pressure (≥100 mm Hg).

Predictors for good clinical outcome

Outcomes were grouped into two categories: good for those patients who were functionally independent (mRS score, 0–2), or poor for those who were dependent or dead (mRS score, 3–6; table 2). Outcomes at 1 month after treatment included an mRS=0 in eight patients, mRS=1 in eight patients, mRS=2 in five patients, mRS=3 in four patients, mRS=4 in five patients, mRS=5 in five patients and death in one patient. Therefore, 21 patients belonged to the good outcome group, and 15 patients to the bad outcome group. Univariate analysis was used to compare patient age, sex, time from onset to admission, NIHSS at admission, initial occlusion site on DSA immediately before thrombolysis, systemic MBP, proximal MBP, distal MBP, difference between the systemic and proximal MBPs, difference between the systemic and distal MBPs, difference between the proximal and distal MBPs, and recanalization state at the end of thrombolysis between the 21 patients with good outcomes and the 15 patients with poor outcomes. Patient age, initial occlusion site, systemic MBP, a difference between the systemic and proximal MBPs, a difference between the systemic and distal MBPs, and recanalization state had p values of <0.10 as measured by univariate analysis. These six items were included in the multivariate analysis (table 2). The multivariate analysis indicated two independent predictors of good outcomes: initial occlusion site (OR, 0.083; p=0.0217) and the difference between the systemic and proximal MBPs (OR, 1.187; p=0.0220).

Table 2

Differences in clinical factors between patients with good (mRS 0–2) and bad (mRS 3–6) outcomes.

Discussion

This study demonstrated a significant difference in the MBP between regions proximal and distal to the embolus in acute major artery occlusion, and the mean difference was ∼60 mm Hg. This pressure gradient exerted hydromechanical forces that pushed the embolus from proximal to distal in the artery. When the clot is disrupted during the clot removal procedure, the hydromechanical force prompts the fragmented clot to migrate into the distal artery. Occlusion caused by the migrated distal embolus is difficult to recanalize by clot retrieval. To prevent distal migration of the clot, proximal movement of the clot is mandatory for retrieval of the whole clot. The stronger hydromechanical force would result in higher compaction of the clot, making it more difficult to remove. During the clot retrieval procedure, a temporary proximal occlusion of the target artery using a balloon catheter is a reasonable method of promoting retrieval of the clot by lowering the pressure gradient between the proximal and distal sites of the clot.

Nogueira et al9 showed that higher systemic blood pressure is associated with lower revascularization rates in the MERCI and Multi MERCI trials. Our study demonstrated that the proximal MBP was significantly higher in patients with high systemic MBP. On the other hand, the univariate analysis revealed that the distal MBP showed no difference between the high and normal systemic MBP groups. Thus, an increase in the systemic blood pressure could potentially increase the hydrodynamic force on the clot from the proximal to the distal sites. Stronger hydromechanical forces produced under higher arterial pressure could result in a more difficult mechanical retrieval, as Nogueira et al speculated.9

The present study demonstrated that factors associated with good outcomes were a difference between the systemic and proximal MBPs and initial occlusion site. The difference between the systemic and proximal blood pressure was identical to the difference in blood pressure between the upper arm and the occlusion site of the intracranial artery. A major cause of the discrepancy in blood pressure values is the narrowing of the inner diameter of the vessel at the sites of pressure measurement. Vessel stenosis or kinking caused by arteriosclerosis within the lumen of the carotid artery to the occlusion site could cause the larger difference between the systemic and proximal MBPs in the bad outcome group.

Study limitation

Different methods were employed for measuring systemic blood pressure, and proximal and distal blood pressures associated with the embolus: the former used a cuff measurement while the latter used a transducer through a microcatheter. Pulse pressure values are reduced through a microcatheter; therefore, in this study, the MBP was used for comparison.14 The MBP obtained by cuff measurement may not be consistent with that obtained by transducer measurement. For all patients, the methods used for blood pressure measurement were consistent, ensuring that unbiased results were obtained.

Summary

Patients with higher systemic MBP showed significantly higher proximal MBP, though no differences in distal MBP were observed when compared with normal systemic MBP. Therefore, a higher systemic blood pressure produced larger hydromechanical forces on the clot, resulting in a more difficult mechanical retrieval.

Key messages

  • When a cerebral embolism occurs, pressure gradients in the arteries between sites proximal and distal to the embolus exert hydromechanical forces that push the embolus distally, and potentially affect successful revascularization during clot removal.

  • We investigated the relationships between blood pressures that occur immediately distal and proximal to the embolus, systemic blood pressure and clinical variables.

  • This study demonstrated that patients with higher systemic blood pressure showed significantly higher proximal blood pressure, though no differences in distal blood pressure were observed when compared with normal systemic blood pressure.

  • Therefore, a higher systemic blood pressure produced larger hydromechanical forces on the clot, and the stronger hydromechanical force could result in higher compaction of the clot, thus making it more difficult to remove.

References

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Footnotes

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Ethics Committee of Nishiogi-chuo Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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